Bone WizardryMEDICAL EDUCATION
⌘ KStart free
Back
On this page
0%
Skip to lesson

Hematology

Platelet disorders: number, function and clinical pattern

Distinguish platelet counting errors, immune and consumptive disorders, marrow causes and receptor defects using clinical context and visible comparisons.

A platelet count answers how many circulating platelets were counted. It does not tell you whether they adhere, activate or aggregate normally, and it does not tell you whether a low count reflects destruction, underproduction or a laboratory artifact. Start by verifying the count and identifying the clinical pattern.

Verify the count, then look at the company it keeps

Thrombocytopenia generally means fewer than 150,000 platelets/µL, although reference ranges and the patient's baseline matter. Petechiae are small, nonblanching skin hemorrhages; mucosal bleeding, epistaxis and heavy menstrual bleeding suggest a primary-hemostasis problem. Deep muscle and joint bleeding more strongly suggest a coagulation-factor disorder, but severe disorders can overlap. Palpable purpura raises a vascular-inflammatory differential rather than automatically identifying a platelet defect.

Review a smear before accepting an unexpected count. EDTA-dependent clumping can produce pseudothrombocytopenia: repeat collection using a suitable alternative anticoagulant and obtain a reliable count with laboratory assistance. Large platelets can also challenge automated counting. A repeat normal count with visible clumps in the original tube is a laboratory phenomenon, not ITP requiring steroids. [12]

Place a low count beside the other findings

Isolated low platelets

Consider ITP, drug-dependent antibodies or inherited thrombocytopenia. Verify the smear and history.

Low platelets plus fragments and hemolysis

Consider TMA or DIC; organ injury and coagulation studies determine urgency and direction.

Several low blood-cell lineages

Consider marrow suppression, infiltration, nutritional disease or hypersplenism.

Normal count with mucosal bleeding

Consider VWD, inherited or acquired platelet dysfunction, and medications.

No box is a final diagnosis. The combination determines which mechanism needs testing. [3] [12] [21]

Bleeding risk is not a universal function of the number alone. Active intracranial or other critical bleeding changes management immediately. Age, trajectory, recent trauma, anticoagulants, planned procedures and platelet function all matter. A count above 150,000 does not exclude a dangerous relative fall in HIT, and a very low count in a well child with ITP does not automatically mandate treatment.

Try it here · Checkpoint 1 of 3

Make your prediction before reading the choices. A first attempt is just a starting point.

Case 1

An asymptomatic adult has an automated platelet count of 48,000/µL. The EDTA smear contains platelet clumps, and a properly corrected citrate-tube count is normal. Which diagnosis is most likely?

Show answer and explanations for case 1

  1. A. ITP requiring immediate corticosteroids (Why this does not fit)

    The reliable repeat count does not show true thrombocytopenia.

  2. B. TTP requiring plasma exchange (Why this does not fit)

    There is no confirmed thrombocytopenia, hemolysis or organ injury.

  3. C. Aplastic anemia (Why this does not fit)

    No multilineage failure or marrow abnormality is present, and the platelet count normalizes with collection correction.

  4. D. Pseudothrombocytopenia (Best answer)

    Clumping in the original sample with a reliable normal repeat count indicates an in-vitro counting artifact.

Takeaway: Verify an unexpected platelet count before assigning disease.

Case sources: [12]

Distinguish immune bleeding from immune thrombosis

ITP: immune destruction with impaired production

ITP usually presents as otherwise unexplained isolated thrombocytopenia, conventionally below 100,000/µL. Antibody-mediated clearance is important, but impaired megakaryocyte platelet production also contributes. Large young platelets may be present. Diagnosis rests on history, examination, CBC and smear with exclusion of alternatives; routine platelet-antibody testing does not provide a necessary definitive confirmation. Review medications and relevant HIV, hepatitis C, autoimmune and other secondary causes. Splenomegaly, anemia unexplained by bleeding, neutropenia or abnormal cells should broaden the investigation. [3]

Adults with minor or no bleeding and counts at least 30,000/µL are often observed, with attention to individual risks. Lower counts more often prompt treatment. Children with newly diagnosed ITP and only skin findings are frequently observed with timely follow-up even when the count is very low. These are different decisions from treatment of critical bleeding, which can require IV corticosteroids, IVIG and platelet transfusion together; do not delay urgently needed platelets simply because immune clearance may shorten their survival. [1] [3]

The 2026 ASH adult primary ITP update changes treatment selection: when initial treatment is needed, it conditionally suggests a corticosteroid-containing combination with rituximab or a thrombopoietic agent, with or without IVIG, over mycophenolate plus corticosteroids or corticosteroids alone. If those combination agents are unavailable, corticosteroids with or without IVIG remain an option. For additional treatment after initial corticosteroids with or without IVIG, it strongly recommends a thrombopoietic agent or conditionally suggests rituximab.

If both are unsuitable or declined, conditional alternatives include a BTK inhibitor, mycophenolate or a SYK inhibitor. These adult recommendations do not replace the pediatric observation approach or the emergency response to critical bleeding. [2]

IVIG can raise counts rapidly when speed matters. Longer-term choices balance sustained response, adverse effects, treatment burden and preferences. Splenectomy remains a possible selected intervention, but is not an automatic early cure and introduces infection and thrombotic risks. Avoid unsupported promises of a fixed cure percentage for every age and disease course. [3]

HIT: a falling count with a prothrombotic antibody

Immune HIT involves platelet-activating antibodies against PF4-heparin complexes. Typical onset is five to ten days after exposure, but recent prior exposure can allow a rapid fall after re-exposure. A greater-than-50% fall matters even when the nadir remains above 150,000/µL. Thrombosis can be venous or arterial. Bleeding is less characteristic than in ITP, but is not impossible. [4]

The 4Ts assess degree of thrombocytopenia, timing, thrombosis and other causes. Scores 0 to 3 are low probability, 4 to 5 intermediate and 6 to 8 high. An accurately assessed low score generally means no HIT testing or empirical HIT treatment. With intermediate or high probability, stop all heparin, select nonheparin anticoagulation appropriate to bleeding risk and clinical stability, and obtain an immunoassay with functional confirmation when indicated.

A positive PF4 immunoassay alone can reflect nonactivating antibodies. Argatroban, bivalirudin and selected other nonheparin agents have different organ-clearance considerations. LMWH is not a safe replacement. Delay warfarin until platelet recovery, and reserve platelet transfusion for relevant bleeding or special high-risk circumstances. [4]

Use organ injury and timing to find the other low-count mechanisms

TTP and HUS are thrombotic microangiopathies with platelet consumption and RBC fragmentation. In TTP, ADAMTS13 activity below 10% supports the diagnosis; obtain a sample before plasma treatment, but do not delay urgent plasma exchange and corticosteroids when immune TTP is strongly suspected. Caplacizumab and rituximab are specialist-directed components of modern care. A historical pentad is not required.

HUS often emphasizes acute kidney injury after Shiga-toxin diarrhea; neurologic involvement does not exclude HUS. STEC-associated care is supportive, with careful fluid and electrolyte management and dialysis when required. Avoid antimotility drugs; antibiotics for suspected STEC can increase HUS risk and are not routine therapy. These cautions do not describe every cause of TMA. [30] [24] Complement-mediated TMA is another mechanism requiring a different evaluation, and normal circulating complement levels do not reliably exclude it. [5] [21]

Three consumptive patterns that should not be collapsed into one
ProcessHelpful contextLaboratory direction
TTPAcute neurologic or other ischemic injury with hemolysisSevere ADAMTS13 deficiency; routine PT/aPTT often normal
Shiga-toxin HUSDiarrheal exposure with prominent kidney injuryHemolysis, thrombocytopenia and evidence of Shiga toxin
DICSepsis, trauma, obstetric emergency or malignancySystemic factor consumption and fibrin turnover; follow PT, fibrinogen, platelets and D-dimer trends

DIC can cause both clotting and bleeding. PT/aPTT may lengthen and fibrinogen may fall, but early values can remain normal. Treat the precipitating disease and use component support for clinical bleeding or relevant procedural needs. A prosthetic valve can fragment RBCs without producing a small-vessel TMA; schistocytes alone do not diagnose TTP. Bite cells and supravitally stained Heinz bodies instead suggest oxidant injury: investigate G6PD deficiency and specific exposures, recognizing that infection itself may trigger hemolysis and standard-use sulfamethoxazole is not classified as high risk by CPIC. An acute normal G6PD result may need reassessment after recovery. [26] [6] [21]

In pregnancy, mild stable thrombocytopenia developing late with no hemolysis, hypertension or liver injury often fits gestational thrombocytopenia. Severe or early thrombocytopenia needs a broader evaluation. HELLP combines hemolysis, increased liver enzymes and low platelets and requires urgent obstetric assessment, especially with hypertension or right-upper-quadrant pain. Delivery can address the obstetric trigger in HELLP; it is not a substitute for TTP treatment. [7]

Maternal ITP can affect neonatal counts through transferred IgG autoantibodies, and maternal count does not precisely predict the newborn's count. Fetal/neonatal alloimmune thrombocytopenia instead targets an inherited fetal platelet antigen absent from the mother; the mother can have a normal count. Severe neonatal thrombocytopenia or bleeding requires urgent specialist assessment, including intracranial bleeding evaluation and appropriate platelet support. Do not confuse this with anti-D-mediated RBC disease. [3] [8]

Underproduction follows chemotherapy, alcohol toxicity, severe nutrient deficiency, aplasia or marrow infiltration, often with other cytopenias. Some medications suppress marrow; others, such as vancomycin or quinine, can provoke abrupt drug-dependent immune destruction. Benzene is a toxic exposure rather than a medication. Portal hypertension can sequester platelets in an enlarged spleen, while liver disease may also reduce thrombopoietin. [31] In rheumatoid arthritis, neutropenia with splenomegaly raises Felty syndrome, with large granular lymphocytic leukemia and medication effects among the alternatives. It is not simply isolated ITP. [9] [19] [22]

Try it here · Checkpoint 2 of 3

Make your prediction before reading the choices. A first attempt is just a starting point.

Case 17

At 33 weeks of pregnancy, a patient develops severe hypertension, right-upper-quadrant pain, hemolysis, increased AST and platelets 58,000/µL. Which syndrome requires urgent obstetric assessment?

Show answer and explanations for case 17

  1. A. Benign gestational thrombocytopenia (Why this does not fit)

    The organ injury and symptoms are incompatible with routine benign gestational thrombocytopenia.

  2. B. ITP as the sole explanation (Why this does not fit)

    ITP alone does not explain hypertension, hemolysis and liver injury.

  3. C. Complement-mediated thrombotic microangiopathy (Why this does not fit)

    That is a pregnancy-associated TMA differential, but severe hypertension and prominent liver symptoms at 33 weeks favor HELLP.

  4. D. HELLP syndrome (Best answer)

    Hemolysis, liver injury and thrombocytopenia in this obstetric context fit HELLP.

Takeaway: Pregnancy-associated organ injury changes the urgency of a low count.

Case sources: [7]

A high count can be reactive, clonal or associated with bleeding

Persistent platelets at least 450,000/µL prompt consideration of thrombocytosis. Iron deficiency, infection, inflammation, tissue injury, malignancy and recent splenectomy can cause reactive increases. Count magnitude alone cannot reliably distinguish reactive from clonal disease. Evaluate the history, smear, iron studies, inflammatory context and persistence after a trigger resolves. [10]

Essential thrombocythemia is a myeloproliferative neoplasm assessed through sustained counts, marrow megakaryocyte morphology, molecular findings such as JAK2, CALR or MPL, and exclusion of competing myeloid disorders. A mutation alone does not replace that integrated diagnosis. Arterial or venous thrombosis and microvascular symptoms can occur. Extreme counts can also cause acquired VWF dysfunction with loss of large functional multimers, creating mucosal bleeding despite an abundance of platelets. [10] [11]

Do not prescribe aspirin solely because the count is high when active bleeding or acquired VWF dysfunction is present. Antiplatelet and cytoreductive decisions depend on thrombosis history, age, genotype, symptoms and bleeding risk. Hydroxyurea or interferon-based therapy may be selected for cytoreduction; anagrelide is an option in particular circumstances. A statistical cutoff or a single number is not a treatment algorithm. [10] [11]

Locate the failed connection in the platelet plug

Wall attachment and platelet-to-platelet attachment use different receptors

Vessel wall → platelet

Exposed collagen binds VWF.
VWF binds platelet GPIb-IX-V.
GPVI also helps platelets recognize collagen.

Adhesion failure: defective VWF or GPIb can impair initial attachment.

Platelet → platelet

Activation changes GPIIb/IIIa, also called integrin αIIbβ3.
Fibrinogen binds activated receptors on adjacent platelets.

Aggregation failure: defective GPIIb/IIIa prevents normal fibrinogen bridging.

VWF attaches a platelet to the injured surface; fibrinogen connects activated platelets to each other. Receptor copy numbers are not numbers of fibrinogen molecules stored on a resting platelet. [12] [13]

Activation recruits additional platelets. Dense granules release ADP, calcium and serotonin; alpha granules contain proteins including VWF, fibrinogen and PF4. Thromboxane A2 is synthesized from arachidonic acid through COX-1 after activation, not simply released as stored granule cargo. ADP acts through P2Y1 and P2Y12: P2Y1 supports calcium signaling, while Gi-coupled P2Y12 reduces cAMP-mediated inhibition and sustains activation. Endothelial prostacyclin and nitric oxide help limit inappropriate platelet activation. [13] [15]

Keep platelet eicosanoids distinct from other prostaglandin functions
MediatorUseful physiological association
TXA2Platelet activation and vasoconstriction
PGI2, prostacyclinEndothelial inhibition of platelets and vasodilation
PGE2Fever signaling is supported by EP3-deficient mouse experiments. Human topical PGE2 experiments also demonstrate increased gastric mucus and cytoprotection; vascular effects depend on receptor and setting. [25] [28]
PGF2αUterine smooth-muscle contraction; human airway experiments also show bronchoconstrictor effects that depend on delivery route. [23] [29]

Bernard-Soulier syndrome usually involves inherited GPIb-IX-V dysfunction with giant platelets and thrombocytopenia. Ristocetin-dependent agglutination is impaired and is not corrected by simply supplying normal plasma. Glanzmann thrombasthenia involves GPIIb/IIIa dysfunction, usually with normal platelet size and count: responses to usual aggregation agonists are impaired, but ristocetin-dependent agglutination is preserved. Dense-granule storage-pool disease can impair secretion and the secondary aggregation response; electron microscopy and secretion studies may help.

Flow cytometry can assess receptor expression, but normal quantity does not exclude a dysfunctional receptor. Severe bleeding in inherited platelet dysfunction may require platelet transfusion; repeated exposure can cause alloimmunization and refractoriness. Selected Glanzmann bleeding, especially with platelet refractoriness, can be treated with recombinant activated VII under specialist direction. [12] [27]

VWD requires antigen, activity and VIII assessment. A normal platelet count is common but not universal, particularly in type 2B. Ristocetin-cofactor assays of plasma VWF and ristocetin-induced agglutination of patient platelets ask different questions. Do not treat every low ristocetin response as the same disease or assume every VWD subtype normalizes with added plasma. Desmopressin is response- and subtype-dependent, and type 2B is a contraindication.

It is ineffective in type 3 and should not be sole therapy for major surgery. VWF concentrate is needed in appropriate nonresponsive or severe settings; tranexamic acid can be useful for selected mucosal bleeding or procedures, with plans based on subtype and bleeding risk. [16] [17]

Acquired dysfunction can exist with a normal count. Uremia impairs platelet hemostasis through multiple mechanisms; dialysis, correction of anemia and short-term desmopressin in selected bleeding or procedural settings can help. Aspirin irreversibly inhibits platelet COX-1 and reduces TXA2 synthesis; recovery depends substantially on new platelets, over their roughly 7-to-10-day lifespan. Platelets retain limited protein synthesis, so saying they can synthesize no protein is inaccurate. Clopidogrel irreversibly inhibits P2Y12, whereas ticagrelor binds reversibly. GPIIb/IIIa inhibitors act at the final fibrinogen-binding stage. Medication history belongs before platelet-function interpretation, and stopping indicated antiplatelet treatment requires a clinical plan. [18] [14] [20]

Try it here · Checkpoint 3 of 3

Make your prediction before reading the choices. A first attempt is just a starting point.

Case 28

A child has lifelong mucosal bleeding, giant platelets, thrombocytopenia and absent ristocetin-dependent agglutination that does not correct with normal plasma. Which receptor complex is most likely defective?

Show answer and explanations for case 28

  1. A. GPIb-IX-V (Best answer)

    The macrothrombocytopenia and failure of plasma correction support Bernard-Soulier syndrome.

  2. B. GPIIb/IIIa (Why this does not fit)

    Glanzmann disease usually has normal platelet count and preserved ristocetin agglutination.

  3. C. P2Y12 alone (Why this does not fit)

    A signaling defect does not best explain this adhesion-specific pattern with giant platelets.

  4. D. GPVI (Why this does not fit)

    GPVI participates in collagen responses, but the giant low-count platelets and absent ristocetin response implicate GPIb-IX-V.

Takeaway: An abnormal platelet receptor cannot be corrected simply by supplying normal plasma VWF.

Case sources: [12]

Practice choosing the platelet mechanism

Case 2

A 31-year-old with newly diagnosed primary ITP has platelets 62,000/µL, a few skin petechiae, no mucosal bleeding and no planned procedure or antithrombotic use. Which approach is usually appropriate?

Show answer and explanations for case 2

  1. A. Routine platelet transfusion to normalize the count (Why this does not fit)

    There is no major bleeding or procedural indication for transfusion.

  2. B. Begin a corticosteroid-containing regimen now (Why this does not fit)

    With platelets above 30,000/µL, only skin findings and no additional risks, observation is generally preferred.

  3. C. Observation with counseling and follow-up (Best answer)

    The count and minor bleeding pattern support observation when additional risk factors are absent.

  4. D. Immediate splenectomy (Why this does not fit)

    An irreversible procedure is not a routine response to this mild initial presentation.

Takeaway: Treatment aims at clinically meaningful bleeding prevention, not automatic count normalization.

Case sources: [1]

Case 3

A well six-year-old has new ITP after a viral illness, platelets 9,000/µL and skin petechiae only. There is no mucosal bleeding, and reliable prompt follow-up is available. Which general management principle applies?

Show answer and explanations for case 3

  1. A. Begin IVIG solely to normalize the platelet count (Why this does not fit)

    For skin-only newly diagnosed pediatric ITP, observation is preferred over IVIG when appropriate follow-up is available.

  2. B. Observation can be appropriate despite the low count (Best answer)

    Pediatric guidelines favor observation for no or minor bleeding, with education and follow-up.

  3. C. Begin corticosteroids solely because the count is below 10,000/µL (Why this does not fit)

    The ASH pediatric recommendation considers bleeding and follow-up rather than using this number alone as a treatment mandate.

  4. D. Give anti-D immunoglobulin solely because the count is below 10,000/µL (Why this does not fit)

    Observation is preferred over anti-D for a child with no or minor bleeding; treatment also has eligibility and toxicity considerations.

Takeaway: Age and bleeding phenotype change the interpretation of the same platelet count.

Case sources: [1]

Case 4

An adult with newly diagnosed primary ITP has platelets 18,000/µL and persistent mucosal bleeding without a critical hemorrhage. Initial treatment is indicated, and rituximab and thrombopoietic therapy are accessible and suitable. Which discussion best reflects the 2026 ASH focused update?

Show answer and explanations for case 4

  1. A. Discuss a corticosteroid-containing combination with rituximab or a thrombopoietic agent (Best answer)

    For adults needing initial treatment, the update conditionally suggests these combinations, with or without IVIG, rather than corticosteroids alone or mycophenolate plus corticosteroids.

  2. B. Recommend corticosteroids alone as preferred over both accessible combination options (Why this does not fit)

    Corticosteroids with or without IVIG remain an alternative when the specified combination drugs are unavailable, but this patient's access and suitability support discussing the conditional combination recommendation.

  3. C. Prefer mycophenolate plus corticosteroids over the specified combinations (Why this does not fit)

    The initial-treatment recommendation favors the rituximab- or thrombopoietic-containing combinations over this option.

  4. D. Recommend immediate splenectomy as the preferred initial treatment (Why this does not fit)

    Splenectomy is a selected later intervention, not the preferred initial approach for this newly diagnosed adult.

Takeaway: Current adult treatment selection should reflect the focused guideline update.

Case sources: [2]

Case 5

A patient with established ITP has intracranial hemorrhage and platelets 3,000/µL. Which response is most appropriate?

Show answer and explanations for case 5

  1. A. Use corticosteroids alone and withhold platelets because they may be rapidly cleared (Why this does not fit)

    Rapid immune clearance does not justify withholding platelet support in an intracranial hemorrhage.

  2. B. Wait for a thrombopoietic agent to act before controlling the hemorrhage (Why this does not fit)

    Slower production support cannot replace immediate emergency measures.

  3. C. Use rituximab alone for immediate hemostatic control (Why this does not fit)

    B-cell therapy does not act quickly enough to replace urgent combined hemostatic support.

  4. D. Urgent platelet support with IVIG and corticosteroid-based emergency treatment (Best answer)

    Critical bleeding requires rapid combined support; short platelet survival does not justify withholding urgently needed platelets.

Takeaway: Critical bleeding is a different decision from treating an isolated low count.

Case sources: [3]

Case 6

An adult with primary ITP needs additional treatment after an initial corticosteroid course. She prefers a nonsurgical approach and is eligible for a thrombopoietic agent. Which mechanism can improve her count?

Show answer and explanations for case 6

  1. A. Depleting CD20-positive B cells (Why this does not fit)

    This is rituximab's mechanism; the question asks about a thrombopoietic agent.

  2. B. Reducing Fc-receptor-mediated clearance through IVIG (Why this does not fit)

    IVIG can reduce immune platelet clearance, but does not explain the production-directed therapy in the stem.

  3. C. Stimulating platelet production through thrombopoietic signaling (Best answer)

    ITP includes impaired production as well as destruction, making production support a disease-directed option.

  4. D. Blocking platelet GPIIb/IIIa to prevent fibrinogen binding (Why this does not fit)

    That inhibits platelet function rather than raising platelet production.

Takeaway: Production-directed therapy addresses a second component of ITP biology.

Case sources: [2] [3]

Case 7

A patient has newly diagnosed isolated thrombocytopenia and otherwise typical ITP findings. Screening identifies previously untreated HIV. Which interpretation is most appropriate?

Show answer and explanations for case 7

  1. A. Classify the finding as an EDTA artifact without reviewing a smear (Why this does not fit)

    HIV does not establish an artifact; a reliable count and the overall clinical pattern still need evaluation.

  2. B. Consider secondary immune thrombocytopenia and address the infection in the care plan (Best answer)

    HIV is a recognized secondary context that can change management.

  3. C. Classify it as primary ITP despite the untreated associated infection (Why this does not fit)

    The infection is a recognized potential secondary cause and belongs in the diagnosis and treatment assessment.

  4. D. Attribute it directly to marrow infiltration without considering immune destruction (Why this does not fit)

    HIV can have several platelet mechanisms, but the otherwise typical isolated ITP presentation makes secondary immune disease a key possibility.

Takeaway: An ITP-like pattern still needs assessment for a relevant secondary cause.

Case sources: [3]

Case 8

A patient referred for presumed ITP has platelets 70,000/µL, neutropenia, an enlarged spleen and atypical circulating lymphocytes. Which next principle is most appropriate?

Show answer and explanations for case 8

  1. A. Broaden evaluation beyond uncomplicated primary ITP (Best answer)

    Other cytopenias, splenomegaly and abnormal cells require assessment for marrow, lymphoid and systemic disease.

  2. B. Begin routine primary-ITP treatment without investigating the other findings (Why this does not fit)

    Additional cytopenias and atypical lymphocytes can indicate a different disorder requiring investigation.

  3. C. Order platelet-antibody testing as the only further diagnostic step (Why this does not fit)

    That test cannot replace evaluation of neutropenia, splenomegaly and abnormal circulating cells.

  4. D. Attribute all abnormalities to splenic pooling without lymphoid assessment (Why this does not fit)

    Splenic pooling may contribute, but atypical lymphocytes and neutropenia require a broader assessment.

Takeaway: The other lineages and the smear can invalidate an initial ITP label.

Case sources: [3] [19]

Case 9

After six days of heparin, a patient’s platelets fall from 390,000 to 175,000/µL and a new pulmonary embolism is diagnosed. Why does the platelet count remain concerning?

Show answer and explanations for case 9

  1. A. Only the absolute nadir should determine HIT probability (Why this does not fit)

    The 4Ts include the percentage decline; a fall from 390,000 to 175,000/µL is approximately 55%.

  2. B. A normal-range nadir outweighs the new thrombotic event (Why this does not fit)

    A substantial relative decline with typical timing and thrombosis remains concerning.

  3. C. Postoperative dilution is sufficient to explain both findings (Why this does not fit)

    Dilution may reduce counts, but does not adequately account for this timing and new PE without further assessment.

  4. D. A fall greater than 50% with typical timing and thrombosis supports HIT suspicion (Best answer)

    The relative decline is clinically meaningful even though the nadir remains above the usual lower reference limit.

Takeaway: HIT assessment depends on the change from baseline.

Case sources: [4]

Case 10

A patient treated with heparin two weeks ago receives heparin again and has an abrupt platelet fall within hours. Which mechanism can explain the rapid timing?

Show answer and explanations for case 10

  1. A. New antibody production from the current dose is required before immune HIT can occur (Why this does not fit)

    Prior sensitization can leave circulating antibodies that permit an immediate response to re-exposure.

  2. B. Direct marrow suppression from the first dose (Why this does not fit)

    Marrow suppression does not explain the recognized rapid immune response after recent heparin exposure.

  3. C. Preexisting HIT antibodies from recent exposure (Best answer)

    Recent sensitization can permit rapid-onset immune HIT on re-exposure.

  4. D. A nonimmune early platelet decline excludes an immune mechanism (Why this does not fit)

    Early nonimmune declines exist, but recent heparin exposure specifically raises the possibility of rapid-onset immune HIT.

Takeaway: Interpret timing against prior exposure, not just the current admission.

Case sources: [4]

Case 11

After surgery and large-volume fluid resuscitation, platelets fall from 240,000 to 110,000/µL on day one. Heparin prophylaxis began after surgery; there was no heparin exposure in the preceding 100 days, no thrombosis, and dilution is a definite alternative explanation. The 4Ts total is 2: thrombocytopenia 2, timing 0, thrombosis 0, other causes 0. What is generally appropriate?

Show answer and explanations for case 11

  1. A. Stop indicated heparin prophylaxis solely because the count fell by more than half (Why this does not fit)

    The complete, reliably assessed low-probability score does not support an empirical HIT pathway solely on the size of the fall.

  2. B. Do not routinely test or empirically treat for HIT (Best answer)

    An accurately assessed low-probability score has a high negative predictive value and avoids misleading tests and unnecessary treatment.

  3. C. Order a PF4 immunoassay despite the reliably assessed low score (Why this does not fit)

    Low pretest probability increases the risk of a misleading positive assay; ASH recommends against routine testing in this situation.

  4. D. Begin therapeutic argatroban automatically (Why this does not fit)

    Empiric treatment adds bleeding risk without supported HIT probability here.

Takeaway: Pretest probability determines whether a HIT assay is useful.

Case sources: [4]

Case 12

A patient with intermediate HIT probability has a weakly positive PF4 immunoassay. The clinical picture has competing explanations. Which further information is particularly useful?

Show answer and explanations for case 12

  1. A. A functional platelet-activation assay interpreted with the clinical probability (Best answer)

    Functional testing helps determine whether the antibodies activate platelets rather than merely bind in an immunoassay.

  2. B. Use immunoassay positivity alone as confirmation of clinical HIT (Why this does not fit)

    Binding antibodies may be nonactivating; functional evidence is especially helpful with intermediate probability and weak positivity.

  3. C. Measure factor VIII activity to establish HIT (Why this does not fit)

    Factor VIII testing evaluates an unrelated coagulation mechanism rather than PF4-dependent platelet activation.

  4. D. Use a repeat platelet count alone to establish antibody pathogenicity (Why this does not fit)

    The count trend informs clinical probability but cannot directly distinguish activating from nonactivating antibodies.

Takeaway: Antibody detection and antibody pathogenicity are related but different questions.

Case sources: [4]

Case 13

A patient with acute confirmed HIT and DVT has platelets 55,000/µL and no major bleeding. Which management principle is correct?

Show answer and explanations for case 13

  1. A. Replace UFH with LMWH as the preferred immune-safe option (Why this does not fit)

    LMWH can cross-react and is not an appropriate substitution in acute HIT.

  2. B. Begin warfarin alone before the platelet count recovers (Why this does not fit)

    Early VKA therapy can worsen acute HIT-associated thrombosis through rapid protein C depletion.

  3. C. Stop heparin without replacement anticoagulation until platelets recover (Why this does not fit)

    Confirmed acute HIT with DVT requires nonheparin anticoagulation despite this low count, absent a prohibitive bleeding circumstance.

  4. D. Use therapeutic nonheparin anticoagulation and defer warfarin until platelet recovery (Best answer)

    Acute HIT requires anticoagulation despite thrombocytopenia, with avoidance of premature VKA therapy.

Takeaway: A low platelet count can coexist with a strong need for anticoagulation.

Case sources: [4]

Case 14

An adult with new symptoms and no prior TTP history with platelets 12,000/µL has fragmented RBCs, hemolysis and transient aphasia. PT is normal, and pretreatment ADAMTS13 activity is 1% with a detected ADAMTS13 inhibitor. Which treatment pathway is most appropriate?

Show answer and explanations for case 14

  1. A. Use recombinant ADAMTS13 prophylaxis alone as for congenital TTP remission (Why this does not fit)

    The inhibitor and acute presentation indicate immune TTP; congenital remission prophylaxis does not replace acute immune TTP care.

  2. B. Use corticosteroids alone while waiting for clinical recovery (Why this does not fit)

    Immunosuppression alone does not replace urgent plasma exchange in this acute immune TTP presentation.

  3. C. Urgent immune TTP therapy including plasma exchange and corticosteroids with specialist adjuncts (Best answer)

    Severe ADAMTS13 deficiency and the TMA phenotype support TTP-specific emergency care.

  4. D. Use caplacizumab alone without plasma exchange or immunosuppression (Why this does not fit)

    VWF-directed platelet inhibition does not remove the inhibitor or provide the complete immune TTP treatment pathway.

Takeaway: TTP treatment follows its mechanism, not merely its platelet count.

Case sources: [5]

Case 15

A child develops oliguria, anemia with schistocytes and thrombocytopenia after a bloody diarrheal illness. Shiga toxin is detected, and ADAMTS13 is not severely deficient. What is most likely?

Show answer and explanations for case 15

  1. A. Immune TTP (Why this does not fit)

    The detected Shiga toxin and absence of severe ADAMTS13 deficiency favor STEC-HUS over immune TTP.

  2. B. Shiga-toxin-associated HUS (Best answer)

    The toxin-associated renal-predominant TMA fits HUS.

  3. C. Primary ITP (Why this does not fit)

    ITP does not account for RBC fragmentation and acute kidney injury.

  4. D. Complement-mediated thrombotic microangiopathy (Why this does not fit)

    A complement-mediated process is another renal TMA differential, but the documented toxin supplies the more specific explanation here.

Takeaway: Platelet consumption and hemolysis require a causal TMA differential.

Case sources: [21] [24]

Case 16

After placental abruption, a patient has diffuse oozing, low platelets, prolonged PT and falling fibrinogen. Which process best explains the combined abnormalities?

Show answer and explanations for case 16

  1. A. DIC triggered by an obstetric emergency (Best answer)

    Systemic coagulation activation consumes platelets and plasma factors.

  2. B. Isolated inherited Glanzmann thrombasthenia (Why this does not fit)

    Glanzmann disease does not explain the acute factor-consumption pattern after abruption.

  3. C. Uncomplicated gestational thrombocytopenia (Why this does not fit)

    That generally lacks bleeding, factor consumption and this acute trigger.

  4. D. Immune TTP (Why this does not fit)

    TTP can cause fragmentation and low platelets, but this acute obstetric trigger with factor consumption favors DIC.

Takeaway: The trigger and plasma-factor changes distinguish DIC from isolated platelet disease.

Case sources: [6] [7]

Case 18

At 37 weeks, an asymptomatic patient has stable platelets of 125,000/µL. Earlier pregnancy counts were normal; blood pressure, AST, creatinine and hemolysis studies are normal. Which explanation is most likely?

Show answer and explanations for case 18

  1. A. Immune TTP (Why this does not fit)

    The mild stable low count without hemolysis or organ injury does not support an acute TMA.

  2. B. Primary ITP (Why this does not fit)

    ITP is possible in pregnancy, but mild isolated late-onset thrombocytopenia with normal earlier counts more often reflects the gestational pattern.

  3. C. Gestational thrombocytopenia (Best answer)

    Mild late-onset isolated thrombocytopenia without organ injury fits the common gestational pattern.

  4. D. HELLP syndrome (Why this does not fit)

    The absence of hemolysis, liver injury and hypertensive findings argues against HELLP.

Takeaway: Mild stable late-pregnancy thrombocytopenia is assessed differently from symptomatic organ injury.

Case sources: [7]

Case 19

A newborn has severe thrombocytopenia and petechiae. The mother’s platelet count is normal, and maternal antibodies recognize a paternal platelet antigen carried by the infant. What is the mechanism?

Show answer and explanations for case 19

  1. A. Reduced production from congenital marrow failure (Why this does not fit)

    The specific maternal platelet alloantibody identifies an immune process rather than a production defect.

  2. B. Fetal/neonatal alloimmune thrombocytopenia (Best answer)

    Maternal alloantibodies target a fetal platelet antigen that the mother lacks.

  3. C. Maternal anti-D causing isolated platelet destruction (Why this does not fit)

    Anti-D targets an RBC antigen rather than a platelet-specific antigen.

  4. D. Neonatal thrombocytopenia from maternal platelet autoantibodies (Why this does not fit)

    Maternal ITP involves autoantibodies; this antibody instead recognizes a fetal antigen absent from the mother.

Takeaway: A normal maternal count does not exclude fetal platelet-directed immune disease.

Case sources: [8]

Case 20

A newborn of a mother with established ITP develops thrombocytopenia. Which maternal immune component can cross the placenta and contribute?

Show answer and explanations for case 20

  1. A. IgG platelet autoantibodies (Best answer)

    Transferred IgG can affect fetal or neonatal platelets in maternal ITP.

  2. B. IgM platelet autoantibodies (Why this does not fit)

    IgM is not normally transported across the placenta like IgG.

  3. C. IgA platelet autoantibodies (Why this does not fit)

    IgA is not the principal placentally transferred antibody class causing this neonatal process.

  4. D. IgE platelet autoantibodies (Why this does not fit)

    IgE is not the placentally transferred effector responsible for this pattern.

Takeaway: Distinguish maternal autoantibody transfer from fetal platelet-antigen alloimmunization.

Case sources: [3] [8]

Case 21

Ten days after cytotoxic chemotherapy, a patient has thrombocytopenia, neutropenia and a low reticulocyte count. The marrow is suppressed without a new infiltrate. Which mechanism best explains the platelet decline?

Show answer and explanations for case 21

  1. A. Isolated immune platelet destruction (Why this does not fit)

    Simultaneous neutropenia and low reticulocytes after cytotoxic treatment favor underproduction rather than an isolated immune platelet disorder.

  2. B. Splenic sequestration (Why this does not fit)

    No enlarged spleen is described, and the observed treatment-associated marrow suppression supplies a direct production explanation.

  3. C. EDTA-dependent pseudothrombocytopenia (Why this does not fit)

    Clumping would require smear evidence and would not explain the associated neutropenia and low reticulocytes.

  4. D. Reduced marrow production (Best answer)

    Several suppressed lineages after chemotherapy support a production problem.

Takeaway: A low platelet count accompanying other production deficits points toward marrow suppression.

Case sources: [3] [12]

Case 22

After vancomycin is restarted, a patient develops abrupt severe thrombocytopenia and mucosal bleeding. Testing identifies vancomycin-dependent platelet antibodies. Which mechanism fits?

Show answer and explanations for case 22

  1. A. Dose-related marrow suppression (Why this does not fit)

    The abrupt fall after re-exposure and drug-dependent antibody evidence favor immune destruction rather than a production effect.

  2. B. PF4-heparin antibody-mediated platelet activation (Why this does not fit)

    That is the HIT mechanism, not the documented vancomycin-dependent reaction.

  3. C. Drug-dependent immune platelet destruction (Best answer)

    The rapid exposure-associated decline and demonstrated antibodies support immune destruction.

  4. D. Sepsis-associated consumptive coagulopathy (Why this does not fit)

    DIC is a differential in an ill patient, but the supplied drug-specific antibody evidence identifies a drug-dependent immune mechanism.

Takeaway: Medication-associated thrombocytopenia can be immune as well as myelosuppressive.

Case sources: [9]

Case 23

A patient with portal hypertension has splenomegaly, stable moderate thrombocytopenia and mild leukopenia. There is no acute hemolysis or new drug exposure. Which mechanism can contribute?

Show answer and explanations for case 23

  1. A. Acute consumptive coagulopathy (Why this does not fit)

    The stable counts and absence of an acute hemolytic or systemic deterioration pattern favor chronic liver-associated sequestration.

  2. B. Splenic sequestration, with possible reduced hepatic thrombopoietin contribution (Best answer)

    Liver disease can lower counts through more than one mechanism and may affect multiple lineages.

  3. C. Primary immune platelet destruction (Why this does not fit)

    An enlarged spleen with mild leukopenia and portal hypertension suggests a broader liver-related mechanism.

  4. D. Cytotoxic suppression of marrow production (Why this does not fit)

    No cytotoxic exposure or direct production evidence is described; the portal-hypertensive spleen provides the more specific explanation.

Takeaway: Hypersplenism and liver signaling can coexist rather than competing as exclusive explanations.

Case sources: [22]

Case 24

A patient with longstanding deforming rheumatoid arthritis has recurrent bacterial infections, neutropenia, splenomegaly and moderate thrombocytopenia. Which syndrome is a key consideration?

Show answer and explanations for case 24

  1. A. Felty syndrome (Best answer)

    RA, splenomegaly and neutropenia form the characteristic association, while other causes including LGL disease need assessment.

  2. B. Uncomplicated isolated ITP (Why this does not fit)

    The prominent neutropenia and splenomegaly are not an isolated ITP pattern.

  3. C. Methotrexate-related marrow suppression (Why this does not fit)

    Medication toxicity remains an alternative to assess, but the longstanding RA, neutropenia and splenomegaly raise the characteristic Felty association.

  4. D. Myelodysplastic neoplasm (Why this does not fit)

    MDS can cause multiple cytopenias, but would need marrow or other clonal evidence; the rheumatoid triad specifically raises Felty syndrome.

Takeaway: The dominant associated lineage can redirect the entire platelet differential.

Case sources: [19]

Case 25

A patient with iron deficiency anemia has platelets 610,000/µL. After iron repletion and control of menstrual loss, the count returns to normal. Which explanation best fits?

Show answer and explanations for case 25

  1. A. Essential thrombocythemia (Why this does not fit)

    The normalization after iron repletion and control of blood loss favors a reactive process over persistent clonal thrombocytosis.

  2. B. Prefibrotic primary myelofibrosis (Why this does not fit)

    This diagnosis requires marrow and clonal evidence; the reversible iron-associated count rise supports a reactive cause.

  3. C. Hereditary thrombocytosis (Why this does not fit)

    A persistent familial pattern would be more suggestive; correction with iron therapy supports a secondary increase.

  4. D. Reactive thrombocytosis (Best answer)

    Resolution with treatment of a plausible trigger supports a reactive process.

Takeaway: Persistence and response to the underlying condition matter more than the peak count alone.

Case sources: [10]

Case 26

A patient has sustained unexplained thrombocytosis, marrow megakaryocytic proliferation with an ET-compatible pattern and a CALR mutation. Competing myeloid disorders have been excluded. Which diagnosis is best supported?

Show answer and explanations for case 26

  1. A. Hereditary thrombocytosis (Why this does not fit)

    The supplied acquired clonal driver and characteristic marrow context support ET; hereditary thrombocytosis requires a different familial and genetic evaluation.

  2. B. Prefibrotic primary myelofibrosis (Why this does not fit)

    This is an important differential, but the stem specifies ET-compatible marrow and exclusion of competing myeloid disorders.

  3. C. Essential thrombocythemia (Best answer)

    Persistent counts, characteristic marrow and a clonal driver support the integrated diagnosis.

  4. D. Reactive thrombocytosis (Why this does not fit)

    A secondary stimulus alone would not account for the integrated clonal and marrow findings provided.

Takeaway: ET is an integrated marrow, molecular and clinical diagnosis.

Case sources: [10]

Case 27

A patient with ET has platelets 1.5 million/µL and new epistaxis. VWF activity is low with loss of high-molecular-weight multimers. Which explanation is most likely?

Show answer and explanations for case 27

  1. A. Aspirin-related platelet dysfunction (Why this does not fit)

    Aspirin may worsen bleeding but does not explain the documented selective loss of large VWF multimers.

  2. B. Acquired von Willebrand dysfunction associated with extreme thrombocytosis (Best answer)

    Loss of effective VWF can produce bleeding despite an excess platelet count.

  3. C. Congenital type 3 VWD (Why this does not fit)

    Type 3 causes profound lifelong VWF deficiency; a new multimer-loss pattern in extreme ET thrombocytosis favors acquired VWF dysfunction.

  4. D. An acquired factor VIII inhibitor (Why this does not fit)

    A factor VIII inhibitor is a secondary-hemostasis disorder and does not explain the specific VWF multimer abnormality.

Takeaway: More platelets can coexist with worse primary hemostasis.

Case sources: [11]

Case 29

A teenager has lifelong mucosal bleeding, normal platelet count and size, failed aggregation with ADP and collagen, and preserved ristocetin agglutination. Which defect best fits?

Show answer and explanations for case 29

  1. A. GPIb-IX-V deficiency in Bernard-Soulier syndrome (Why this does not fit)

    That would impair ristocetin agglutination and commonly produce giant low-count platelets.

  2. B. Complete absence of plasma VWF (Why this does not fit)

    Severe VWF absence would impair ristocetin-dependent agglutination.

  3. C. Dense-granule storage-pool deficiency (Why this does not fit)

    A secretion defect more often impairs the secondary response; the broad aggregation failure with preserved ristocetin response favors Glanzmann.

  4. D. GPIIb/IIIa dysfunction in Glanzmann thrombasthenia (Best answer)

    The platelet-to-platelet fibrinogen bridge is impaired while the ristocetin-dependent adhesion pathway remains functional.

Takeaway: Ristocetin preserves a useful distinction between adhesion and aggregation disorders.

Case sources: [12]

Case 30

A patient with normal platelet count has mucosal bleeding and reduced ATP release on secretion testing. Electron microscopy shows few dense granules. What is the most likely defect?

Show answer and explanations for case 30

  1. A. An isolated dense-granule secretion defect with normal granule number (Why this does not fit)

    The electron microscopy demonstrates reduced granule number, identifying a storage-pool deficiency rather than secretion machinery alone.

  2. B. GPIb-IX-V deficiency (Why this does not fit)

    An adhesion-receptor defect does not explain reduced dense granules and ATP release.

  3. C. Dense-granule storage-pool deficiency (Best answer)

    Reduced granule content explains impaired secretion-dependent recruitment and secondary aggregation.

  4. D. GPIIb/IIIa deficiency (Why this does not fit)

    An aggregation-receptor defect can impair function, but the demonstrated dense-granule deficit identifies a different mechanism.

Takeaway: Platelet dysfunction can arise from what a platelet releases, not only what it binds.

Case sources: [12]

Case 31

A patient with mucosal bleeding has VWF that binds platelets excessively at low ristocetin concentrations, intermittent thrombocytopenia and a confirmed type 2B VWF variant. Which treatment concern is relevant?

Show answer and explanations for case 31

  1. A. Desmopressin fails only because type 2B lacks all stored VWF (Why this does not fit)

    Type 2B produces abnormal VWF with excessive platelet affinity; release can worsen platelet clearance.

  2. B. Desmopressin can worsen thrombocytopenia by releasing abnormal VWF (Best answer)

    Excess platelet binding is the key type 2B mechanism.

  3. C. Desmopressin predictably raises the platelet count by reducing VWF binding (Why this does not fit)

    It releases the abnormal VWF and can instead worsen thrombocytopenia.

  4. D. Desmopressin directly replaces normal VWF in plasma (Why this does not fit)

    It promotes endogenous VWF release rather than supplying a normal replacement concentrate.

Takeaway: A VWF disorder can affect both function and platelet number.

Case sources: [16] [17]

Case 32

A patient with severe uremia has persistent oozing after a procedure despite normal platelet count and normal PT/aPTT. No antiplatelet drug is present. Which explanation is most likely?

Show answer and explanations for case 32

  1. A. Acquired qualitative platelet dysfunction (Best answer)

    Uremia can impair hemostasis without a low count or abnormal plasma clotting screen.

  2. B. Acquired factor VIII inhibition (Why this does not fit)

    Clinically significant factor VIII inhibition usually prolongs aPTT and does not best fit the supplied normal coagulation screen with uremia.

  3. C. Immune thrombocytopenia (Why this does not fit)

    The reliable normal platelet count argues against a quantitative immune platelet disorder.

  4. D. Disseminated intravascular coagulation (Why this does not fit)

    No consumptive laboratory or acute systemic trigger pattern is supplied; uremia can impair platelet function with these normal screening results.

Takeaway: Normal count and clotting times do not rule out an acquired platelet-function defect.

Case sources: [12] [18]

Case 33

A patient takes aspirin daily and has normal platelet count but impaired thromboxane-dependent platelet responses. Which mechanism explains the effect?

Show answer and explanations for case 33

  1. A. Direct reversible blockade of GPIb binding to VWF (Why this does not fit)

    Aspirin inhibits COX-1-dependent TXA2 synthesis rather than reversibly blocking the VWF adhesion receptor.

  2. B. Reversible inhibition of platelet COX-1 (Why this does not fit)

    Aspirin irreversibly acetylates COX-1, unlike the reversible inhibition produced by many other NSAIDs.

  3. C. Irreversible inhibition of P2Y12 (Why this does not fit)

    That is the mechanism of clopidogrel's active metabolite, not aspirin.

  4. D. Irreversible inhibition of platelet COX-1 (Best answer)

    Reduced TXA2 synthesis persists beyond plasma drug clearance because the target is slowly renewed.

Takeaway: Separate the enzyme target from granule contents and platelet number.

Case sources: [13] [14] [20]

Case 34

After coronary stenting, a patient receives clopidogrel. Which platelet signal is directly inhibited by its active metabolite?

Show answer and explanations for case 34

  1. A. Fibrinogen binding directly to GPIIb/IIIa (Why this does not fit)

    GPIIb/IIIa inhibitors directly block this final interaction; clopidogrel acts on upstream ADP signaling.

  2. B. COX-1-dependent thromboxane synthesis (Why this does not fit)

    Aspirin inhibits COX-1; clopidogrel instead inhibits the ADP receptor P2Y12.

  3. C. ADP signaling through P2Y12 (Best answer)

    Clopidogrel irreversibly inhibits this ADP receptor pathway.

  4. D. VWF binding through GPIb-IX-V (Why this does not fit)

    That adhesion receptor is not clopidogrel’s direct target.

Takeaway: P2Y12 inhibition interrupts activation signaling before final fibrinogen bridging.

Case sources: [14] [15]

Case 35

During a selected coronary intervention, a patient receives a GPIIb/IIIa inhibitor. Which interaction is most directly blocked?

Show answer and explanations for case 35

  1. A. COX-1-dependent thromboxane synthesis (Why this does not fit)

    COX-1 is aspirin’s target, while the named inhibitor directly blocks GPIIb/IIIa ligand binding.

  2. B. Fibrinogen binding between adjacent activated platelets (Best answer)

    Activated αIIbβ3 supports the platelet-to-platelet bridge targeted by these drugs.

  3. C. VWF binding to GPIb-IX-V (Why this does not fit)

    That is the vessel-to-platelet adhesion interaction, whereas GPIIb/IIIa inhibition blocks aggregation between platelets.

  4. D. ADP binding to P2Y12 (Why this does not fit)

    P2Y12 antagonists block ADP signaling; the drug in this stem acts at the final fibrinogen-binding receptor.

Takeaway: Locate the final aggregation receptor on the platelet-to-platelet connection.

Case sources: [12] [14]

Case 36

A laboratory studies platelet activation after vascular injury. ADP released from dense granules stimulates a Gi-coupled receptor and reduces inhibitory cAMP signaling. Which receptor is involved?

Show answer and explanations for case 36

  1. A. P2Y12 (Best answer)

    The Gi-coupled ADP receptor sustains activation partly by reducing cAMP-mediated inhibition.

  2. B. P2Y1 as the Gi-coupled receptor (Why this does not fit)

    P2Y1 is primarily Gq-coupled and supports calcium signaling.

  3. C. GPIb as an ADP receptor (Why this does not fit)

    GPIb binds VWF for adhesion rather than serving as this ADP receptor.

  4. D. GPIIb/IIIa as the receptor that recognizes ADP directly (Why this does not fit)

    This integrin binds ligands such as fibrinogen after activation; it is not the stated ADP receptor.

Takeaway: ADP uses distinct receptors for complementary activation signals.

Case sources: [13] [15]

Case 37

During a febrile infection, an adult develops DAT-negative hemolysis with bite cells and Heinz bodies on a supravital stain. Platelets and coagulation studies are normal. G6PD activity is normal during marked reticulocytosis. Which interpretation best fits?

Show answer and explanations for case 37

  1. A. The acute normal activity excludes G6PD deficiency (Why this does not fit)

    Selective destruction of older deficient cells and enrichment with younger cells can mask the deficiency.

  2. B. An oxidative RBC disorder remains possible and may require repeat enzyme testing after recovery (Best answer)

    The morphology suggests oxidant injury, while the timing limits interpretation of G6PD activity.

  3. C. The findings establish immune TTP (Why this does not fit)

    The platelet count is normal and the smear describes oxidant inclusions and bite cells rather than a platelet-consuming fragmentation syndrome.

  4. D. Pyruvate kinase deficiency is established by the normal G6PD result (Why this does not fit)

    A normal acute G6PD assay does not diagnose pyruvate kinase deficiency; the oxidant morphology and reticulocytosis call for careful reassessment.

Takeaway: Use the RBC morphology and enzyme-testing context when the low-count TMA pattern is absent.

Case sources: [21] [26]

Case 38

A child with confirmed quantitative VWD has mucosal bleeding, low VWF antigen and activity, a normal platelet count, normal PT and a prolonged aPTT. Factor VIII activity is reduced. Which VWF function explains the aPTT result?

Show answer and explanations for case 38

  1. A. Stabilizing circulating factor VIII (Best answer)

    Reduced VWF permits faster factor VIII clearance, which can prolong the intrinsic-pathway assay.

  2. B. Binding GPIb for initial platelet adhesion (Why this does not fit)

    That function explains primary-hemostatic bleeding but does not directly explain reduced plasma VIII and the aPTT change.

  3. C. Bridging adjacent platelets through GPIIb/IIIa (Why this does not fit)

    Fibrinogen primarily supplies that aggregation bridge; the aPTT change here is related to factor VIII stabilization.

  4. D. Cleaving ultra-large VWF multimers (Why this does not fit)

    ADAMTS13 performs that cleavage; deficiency causes TTP rather than the supplied VWD factor VIII pattern.

Takeaway: VWF contributes to platelet adhesion and factor VIII survival through separate functions.

Case sources: [16] [17]

Case 39

An adult with primary ITP begins a corticosteroid-containing treatment regimen. Which effect most directly reduces immune platelet destruction?

Show answer and explanations for case 39

  1. A. Activation of the thrombopoietin receptor (Why this does not fit)

    Thrombopoietic agents support production through that pathway; this is not the corticosteroid's principal immune effect.

  2. B. Selective binding to CD20 (Why this does not fit)

    CD20 binding is rituximab's direct target, rather than corticosteroid pharmacology.

  3. C. Suppression of immune activity and macrophage-mediated platelet clearance (Best answer)

    Corticosteroids can reduce immune destruction, while impaired production remains another component of ITP biology.

  4. D. Inhibition of platelet GPIIb/IIIa (Why this does not fit)

    This impairs aggregation and does not explain reduced immune platelet clearance.

Takeaway: Distinguish immune-clearance treatment from production support and antiplatelet therapy.

Case sources: [3]

Sources

  1. ASH 2019 guidelines for immune thrombocytopenia (2019)

    Observation thresholds, pediatric management and diagnostic context; adult treatment selection superseded where addressed by the 2026 update.

  2. ASH 2026 ITP guidelines: Summary of changes (2026)

    Official focused update for initial and second-line adult primary ITP therapy; no unpublished journal DOI is invented.

  3. Updated international consensus report on investigation and management of primary ITP (2019)

    Diagnostic exclusions, secondary causes, emergency IVIG/steroid/platelet support and maternal/neonatal immune disease.

  4. ASH 2018 guidelines: Heparin-induced thrombocytopenia (2018)

    4Ts scoring, immune and functional tests, nonheparin treatment and platelet transfusion exceptions.

  5. ISTH 2025 focused update of TTP management guidelines (2025)

    ADAMTS13-related TTP and urgent specialist-directed therapy.

  6. BSH: Diagnosis and management of disseminated intravascular coagulation (2009)

    Consumption, serial laboratory trends and bleeding-directed support; obsolete drug recommendations not adopted.

  7. ASH: Thrombocytopenia in pregnancy (2022)

    Gestational thrombocytopenia versus HELLP and other pregnancy-associated TMAs.

  8. ICTMG: Fetal and neonatal alloimmune thrombocytopenia, evidence-based recommendations (2019)

    Maternal anti-platelet alloantibodies, fetal/neonatal bleeding risk and urgent management.

  9. NEJM: Vancomycin-induced immune thrombocytopenia (2007-03-01)

    Primary evidence for drug-dependent platelet antibodies and severe bleeding.

  10. NCI: Myeloproliferative Neoplasms Treatment, PDQ

    Persistent thrombocytosis, ET diagnosis, molecular/marrow assessment and treatment options.

  11. ASH Blood: How I treat essential thrombocythemia (2016)

    Thrombosis risk, acquired VWF dysfunction, bleeding and individualized antiplatelet/cytoreductive treatment.

  12. ARUP Consult: Functional Platelet Disorders

    Smear, inherited receptor defects, secretion tests, ristocetin patterns and obsolete bleeding time.

  13. ASH: Understanding and Evaluating Platelet Function (2010)

    Adhesion, activation, granules, newly synthesized thromboxane and endothelial inhibition.

  14. ASH Blood: How I use laboratory monitoring of antiplatelet therapy (2017)

    COX-1, P2Y receptors, thromboxane and drug targets.

  15. ASH Blood: The platelet P2Y12 receptor for ADP, congenital and drug-induced defects (2011)

    Gi-coupled P2Y12 signaling and platelet activation.

  16. ASH ISTH NHF WFH 2021 guidelines on diagnosis of VWD (2021)

    VWF antigen, activity and VIII testing; type 2B and differential diagnosis.

  17. ASH ISTH NHF WFH 2021 guidelines on management of VWD (2021)

    Subtype-dependent desmopressin, antifibrinolytic and concentrate use.

  18. ASH Blood: Desmopressin in the treatment of bleeding disorders (1997)

    Short-term hemostatic use in uremia; historical bleeding-time testing recommendations not adopted.

  19. ASH Blood: How we evaluate and treat neutropenia in adults (2014)

    Felty syndrome and overlap with large granular lymphocytic leukemia.

  20. ASH Blood: Platelet activation and inhibition in PV and ET (2013)

    Irreversible aspirin effect, limited COX resynthesis and thrombocytosis-associated bleeding considerations.

  21. ARUP Consult: Hemolytic Anemias

    TMA morphology, Shiga-toxin HUS and distinction from other fragmentation causes.

  22. AASLD: Peri-procedural management of bleeding risk in cirrhosis

    Cirrhosis-associated thrombocytopenia and limitations of INR-based bleeding assessment.

  23. Human myometrium study: In-vitro characterization of prostanoid receptors at term pregnancy (1993)

    Primary human-tissue evidence for prostanoid-dependent uterine effects.

  24. CDC: Signs of hemolytic uremic syndrome (2024-05-14)

    Shiga-toxin-associated HUS, kidney injury and possible decreased awareness.

  25. Nature: Impaired febrile response in mice lacking the PGE receptor EP3 (1998-09-17)

    Primary mechanistic evidence for PGE2-mediated fever through EP3; animal experiment, not a human treatment trial.

  26. Expanded CPIC guideline for medication use in the context of G6PD genotype (2023)

    Drug-specific oxidant risk, variable phenotype in heterozygotes and G6PD testing.

  27. WFH: Platelet Function Disorders (2008)

    Inherited receptor and granule defects, platelet transfusion, alloimmunization and selected Glanzmann rFVIIa use; historical mechanism/supportive-care reference, not current dosing guidance.

  28. Gastric cytoprotection in man by prostaglandin E2 (1981)

    Primary human topical PGE2 experiment showing increased gastric mucus and cytoprotection.

  29. Newball et al.: Prostaglandin F-2 alpha functions as a local hormone on human airways (1980-08)

    Primary human airway study of route-dependent PGF2-alpha bronchoconstriction.

  30. CDC: Information for clinicians, E. coli infection (2024-05-14)

    STEC antimicrobial/antimotility cautions and supportive HUS care.

  31. Goulis et al.: Thrombopoietin concentrations in cirrhosis and after liver transplantation (1999-05)

    Primary human cohort supporting deficient thrombopoietin as a contributor to cirrhotic thrombocytopenia.

Return to lesson title

Search Bone Wizardry

Quick links
↑ ↓ Navigate Enter Open Esc CloseBrowse the library ↗