Master the 3-step assembly line. Learn what breaks when receptors fail.
A 45-year-old man presents with spontaneous bruising, petechiae, and gum bleeding. Labs show platelets 35,000 (ref: 150,000-400,000). He denies recent infections or medications. Which is the most likely diagnosis?
Clinical Images
π· Petechiae: pinpoint non-blanching spots Β· tap to expand
π· Purpura: non-blanching purple patches Β· tap to expand
A) Thrombocytosis
B) Immune thrombocytopenia (ITP)
C) Thrombotic microangiopathy
D) Bernard-Soulier syndrome
Thrombocytopenia (<150k) with petechiae + mucosal bleeding
ITP is the most common cause (MCC: virus, then drugs). Antibodies attack platelet surface antigens. 90% resolve in kids, 90% chronic in adults. Never transfuse unless surgery or count <10k (transfused platelets get destroyed faster).
Build The Diagnosis
Fill the four blanks from the word bank to complete the case. Five cases. Wrong picks reveal the right one with the mechanism.
Case Builder
Tap a blank to activate it, then tap a word from the bank below. The blank fills. Hit Check Diagnosis when all four are placed.
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Word Bank
From the Attending
Every platelet vignette clinical medicine write is the same Mad Lib: platelet count + smear feature + coag profile + clinical trigger → diagnosis. Once you can build the sentence from a word bank, you can read it backwards from any board stem. Low + schistocytes + normal coags + neuro signs = TTP. Normal + bleeding + normal coags + ristocetin fail = vWD. Low + heparin day 7 + new clot = HIT. Both prolonged + low fibrinogen + sepsis = DIC.
Thrombocytosis vs Thrombocythemia: Where's the Line?
Thrombocytosis = slight β in platelet count. Benign. Usually secondary.
Thrombocythemia = platelet count >2 SD above normal. Pathologic. Can cause clots.
Board trap: MCC of thrombosis is stasis, NOT thrombocytosis. A patient with mildly elevated platelets but a long plane ride is far more likely to clot than someone with severely elevated platelets who's ambulatory.
Classification: A subtype of hemolytic anemia (β bilirubin, β haptoglobin, β LDH)
Types: TTP, HUS, DIC, prosthetic heart valve
Key distinction
ALL thrombotic microangiopathy can cause MAHA, but NOT all MAHA is caused by thrombotic microangiopathy (e.g., prosthetic valve clots RBCs directly).
From the Attending
Thrombotic microangiopathy (TMA) is a clinical syndrome, not a single disease. The trio: schistocytes + thrombocytopenia + organ damage. Pick the disease by the organ that's most loud. Brain → TTP (FAT-RN: Fever, Anemia, Thrombocytopenia, Renal, Neuro · classic pentad, often partial). Kidney + child + diarrhea → HUS (Shiga toxin from EHEC O157:H7). Bleeding + clotting + low fibrinogen + high D-dimer → DIC.The smear (schistocytes everywhere) confirms TMA; the organ pattern names which one.
Often triggered by infection (patients don't remember being sick). 90% resolve in children, 90% become chronic in adults.
Can precede SLE in adolescent females.
Treatment: Corticosteroids first-line
DO NOT transfuse platelets (they get destroyed faster). Exception: surgery or count <10k.
3. Infection
Mechanism: BM suppression or hypersplenism
Sepsis: 48% of patients develop thrombocytopenia
Viruses: Parvovirus B19, Hepatitis C, Hepatitis E
4. Medication
AZT (zidovudine) β’ Vinblastine β’ Chloramphenicol β’ Benzene
Impair platelet production or cause immune destruction
5. HIT (Heparin-Induced Thrombocytopenia)
Critical pathophysiology: Autoimmune disorder, ~5% of heparin patients, dose-independent
IgG binds to heparin-PF4 complex β activates platelets β BOTH arterial AND venous thrombosis
HIT-2 (pathologic): 3-10 days after heparin start, thrombosis risk
HIT-1 (benign): Platelet clumping day 1-2, just monitor
From the Attending
The five causes map to one question on every stem: destruction vs production vs sequestration vs dilution vs consumption. ITP = autoimmune destruction, isolated thrombocytopenia, normal smear, kids post-viral or adults idiopathic. TTP = ADAMTS13 deficiency, schistocytes, neuro signs. DIC = consumption + clotting + bleeding, low fibrinogen, high D-dimer. HIT = autoimmune, day 5·10 of heparin, paradoxical thrombosis (the patient clots, doesn't bleed). Drug-induced = quinine, vancomycin, sulfa · stop the drug, count recovers. The board hook on HIT is "patient on heparin now clotting, not bleeding" · stop heparin, switch to argatroban or bivalirudin (NOT warfarin alone → skin necrosis).
The Platelet Assembly Line: 3 Steps to Build a Plug
Click each step to see what happens, what molecules are involved, and what breaks when components fail.
1
Adhesion
2
Degranulation
3
Aggregation
Step 1: Adhesion (The First Responder)
Injury exposes subendothelial collagen. Platelets must stick to the wound.
Key players:
Collagen (in subendothelium)
vWF (von Willebrand Factor)
GpIb receptor (on platelet)
The dance: Collagen β vWF binds collagen β GpIb on platelet binds vWF β platelet stuck to wall
Platelets must cross-link to each other to form a stable plug.
The key cross-linker:
Fibrinogen (40k-80k copies per platelet)
GpIIb/IIIa receptor (binds fibrinogen)
The mechanism: GpIIb/IIIa on one platelet binds fibrinogen β fibrinogen binds GpIIb/IIIa on adjacent platelet β platelets bridge together β plug forms
Defective GpIIb/IIIa βGlanzmann Thrombasthenia (no fibrinogen bridge, platelets can't stick to each other, mucocutaneous bleeding)
Prostaglandin Actions: Quick Reference
Prostaglandin
Actions
Prostacyclin (PGI2)
β Platelet aggregation, vasodilation (produced by endotheliumβthe body's "brake" on clotting)
Do NOT transfuse unless absolutely necessary (can worsen)
vs HUS
TTP = neuro + renal. HUS = renal only (especially in kids after diarrhea)
Board trap
TTP vs ITP: Both have β platelets. TTP has schistocytes (MAHA). ITP does not. This is the key distinction.
From the Attending
Four-receptor map you'll get tested on: GpIb · binds vWF, broken in Bernard-Soulier (BIG platelets, BIG bleeding). GpIIb/IIIa · binds fibrinogen, broken in Glanzmann (normal-size platelets, no aggregation). ADP receptor (P2Y12) · target of clopidogrel/ticagrelor. TXA2 pathway (COX-1) · target of aspirin. Stem says "platelet count normal, PT/PTT normal, but bleeding time is up"? You're looking at a receptor or pathway defect, not a count problem. vWD is the most common inherited bleeding disorder · tracks normal counts but abnormal vWF-dependent aggregation (ristocetin).
Matching Game: Receptor β Disease
Match the broken receptor to the disease. Click an option and see if you're correct.
Memory Hooks: The Sticky Mnemonics
Tap to reveal:
Bernard-Soulier = Big and Sad
Giant platelets can't stick to collagen (defective GpIb = can't bind vWF). They're "big" (literally) and "sad" (can't do their job).
Glanzmann = Glue-less
Normal platelets but NO fibrinogen bridge (defective GpIIb/IIIa). Imagine soldiers with no rope to tie them togetherβthey all stand alone.
vWF is the VIP Escort
vWF has TWO jobs: (1) escorts Factor VIII to the party, (2) holds platelets to collagen. Without the escort, the guest (Factor VIII) never arrives AND the bouncer (platelet) can't work the door.
ITP vs TTP: Destroy vs Overshoot
ITP = Immune (antibodies EAT platelets, destructive). TTP = Thrombotic (platelets FORM unwanted clots, overproduction). One breaks them, the other overuses them.
Villain Cards: The Platelet Criminals
Tap each villain to flip and reveal their signature crime, weapon, and board trap.
π₯
ITP
The Immune Assassin
tap to reveal
ITP
WeaponIgG antibodies vs platelet surface antigens
Trace ItAntibody-coated platelets eaten by splenic macrophages
SmearNormal RBCs (no schistocytes)
Key labsIsolated low platelets. PT/PTT normal.
TxSteroids first. Never transfuse platelets (destroyed faster).
Microangiopathic process: TTP, HUS, or DIC. Urgent workup.
TTP. Treat with plasmapheresis immediately. No platelet transfusions.
HUS. Supportive care. No antibiotics (increase toxin release). Dialysis if needed.
DIC. Treat the underlying cause (sepsis, abruption, AML-M3). FFP + cryo + platelets as needed.
Isolated low platelets, normal smear. Was patient recently started on heparin?
HIT (heparin-induced thrombocytopenia). Use the 4T score. Stop ALL heparin forms including flushes. Start argatroban or bivalirudin. Do NOT start warfarin until platelets recover above 150k.
Drug-induced ITP. Stop the offending drug. Platelets recover in days to weeks.
Hypersplenism. Platelets are trapped, not destroyed. Treat the underlying cause (cirrhosis, portal hypertension, lymphoma).
ITP. Check H. pylori, HIV, HCV first. First-line: steroids + IVIG. Splenectomy for refractory cases. Anti-D immunoglobulin if Rh-positive and not splenectomized.
Platelet dysfunction, not low count. Check further:
von Willebrand Disease. Most common inherited bleeding disorder. Type 1: low vWF. Type 2: dysfunctional vWF. Type 3: absent vWF. Treat type 1 with DDAVP.
Drug-induced platelet dysfunction. ASA blocks COX (no TXA2). Clopidogrel blocks P2Y12 (no ADP response). Abciximab/eptifibatide block fibrinogen binding. Effects persist until new platelets form (7-10 days for ASA).
Uremic platelet dysfunction. Uremic toxins impair GpIb-vWF binding. Treat with dialysis, DDAVP, or cryoprecipitate.
Test Your Knowledge
5 random questions from a pool of 12+
From the Attending
Quiz strategy for platelet stems: (1) Read the platelet count first. Normal + bleeding → receptor/pathway or vWD. Low → destruction/production/consumption. (2) Read the smear next. Schistocytes → TMA family (TTP, HUS, DIC). Giant platelets → Bernard-Soulier or ITP. (3) Read the coags. Isolated thrombocytopenia + normal PT/PTT → ITP. Both up + low fibrinogen + high D-dimer → DIC. (4) Match the trigger. Heparin 5·10 days + new clot → HIT. Post-viral kid with low platelets → ITP. Diarrhea + AKI + schistocytes → HUS. Pregnant patient with hypertension + low platelets → HELLP. Four reads, every time.
Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last updated July 1, 2026 at 10:03 PM ET
Bone Wizardry is an independent educational resource for visual learning in the medical sciences. It is not affiliated with, endorsed by, or sponsored by any licensing or examination board, contains no real or recalled examination questions, and does not guarantee any educational or examination outcome.
