Primary Hemostasis: The First Line
When a blood vessel gets cut, the body launches a three-act response:
Act 1 · Vasoconstriction: Smooth muscle squeezes the vessel shut. Sympathetic nerves fire. This buys time. The classic board pearl: a patient with an epidural hematomaMiddle meningeal artery tear, usually from temporal bone fracture. The lucid interval happens because vasoconstriction temporarily stops the bleed · then it gives way. has a "lucid interval" because vasoconstriction temporarily holds the arterial bleed. Then it fails.
Act 2 · Platelet Plug (primary hemostasis): Platelets rush to the scene, stick to exposed collagen, activate, and clump together. This is today's main event.
Act 3 · Fibrin Clot (secondary hemostasis): The coagulation cascade lays down a fibrin mesh to reinforce the platelet plug. That's a different page.
Platelet basics: Born from megakaryocytes in the bone marrow. Stimulated by thrombopoietin (from the liver). Survive 4,7 days. Normal count: 150K,350K. Above 350K = thrombocytosis. Below 150K = thrombocytopenia.
Bleeding patterns tell you where the problem is:
Petechiae
Tiny pinpoint dots (1,2mm). Platelet problem. Think: "tiny cells, tiny dots." Won't blanch with pressure.
tap to reveal
Purpura
Larger purple patches (3mm,1cm). Can be palpable (vasculitis) or flat (platelet issue). Palpable purpura = inflammation in vessel walls.
tap to reveal
Ecchymoses
Bruises (>1cm). Can be from platelet OR coagulation factor problems. Less specific on its own.
tap to reveal
Hemarthrosis
Bleeding INTO joints. This is a coagulation factor problem (hemophilia), NOT platelets. If you see joint bleeds, think secondary hemostasis.
tap to reveal
How Platelets Build a Plug
Three steps, three receptors. Tap through each step to watch the plug form.
Vessel injury: The endothelium is breached, exposing subendothelial collagen to the bloodstream. Platelets float past freely · for now.
Memory anchor: The receptors go in alphabetical order of the Roman numeral:
GpIb = adhesion (step 1),
GpIIb/IIIa = aggregation (step 3).
I before II. Stick before clump.
When Platelets Break
Three inherited disorders, three different problems. Each one breaks a specific step in plug formation.
Bernard-Soulier Syndrome
What's broken
GpIb receptor · platelet can't grab vWF, so it can't stick to the wall
Step disrupted
Step 1 · Adhesion
Inheritance
Autosomal recessive
Platelet size
GIANT platelets (bigger than normal)
Platelet count
LOW (thrombocytopenia)
Bleeding time
Prolonged
PT / PTT
Normal / Normal
Board clue
"Giant platelets" + low count + prolonged bleeding time
Glanzmann Thrombasthenia
What's broken
GpIIb/IIIa receptor · fibrinogen can't bridge platelets together
Step disrupted
Step 3 · Aggregation
Inheritance
Autosomal recessive
Platelet size
Normal
Platelet count
Normal
Bleeding time
Prolonged
PT / PTT
Normal / Normal
Board clue
Normal count + normal size + NO aggregation on testing. Platelets stick to the wall fine but can't clump.
von Willebrand Disease
What's broken
von Willebrand Factor · the glue between collagen and GpIb is missing/defective
Step disrupted
Step 1 · Adhesion (plus secondary effect: less Factor VIII)
Inheritance
Autosomal DOMINANT (most common inherited bleeding disorder)
Platelet size
Normal
Platelet count
Normal
Bleeding time
Prolonged
PT / PTT
Normal PT / Elevated PTT (because less vWF = less Factor VIII protection)
Classic presentation
Kid with nosebleeds, dental bleeding, heavy periods. Family history.
Diagnostic test
Ristocetin cofactor assay · ristocetin activates vWF binding. Low activity = vWD.
Treatment
Mild = DDAVP (desmopressin, releases stored vWF). Moderate = cryoprecipitate. Severe = FFP.
Quick comparison: Bernard-Soulier = big but few platelets. Glanzmann = normal everything except aggregation. vWD = normal platelets + elevated PTT (the only one that touches the coagulation cascade).
Thrombocytopenia: Why Platelets Drop
Low platelets (<150K). The cause changes the treatment entirely. Tap each category.
MCC: Viral
Most common cause overall. Viruses suppress bone marrow or trigger immune destruction. Parvo B19, Hep C, Hep E, HIV.
tap to reveal
Drugs
Second most common. AZT (zidovudine), vinblastine, chloramphenicol, benzene. These suppress marrow production.
tap to reveal
Consumption
Platelets used up faster than made. DIC (everything activates), TTP (microthrombi), HUS (renal microthrombi). Low platelets + schistocytes = consumption.
tap to reveal
Autoimmune (ITP)
Antibodies against platelet surface antigens. Isolated thrombocytopenia · everything else is normal. Treat: steroids first, then IVIG, splenectomy if refractory.
tap to reveal
TTP · The Pentad: ADAMTS13 deficiency (can't break down large vWF multimers) → microthrombi everywhere. Classic pentad:
thrombocytopenia,
MAHA (schistocytes),
fever,
renal failure,
neuro symptoms.
Treatment: plasmapheresis (replaces ADAMTS13). Do NOT give platelets · feeds the fire.
TMA vs MAHA
These get confused constantly. Here's the clean separation.
TMA (Thrombotic Microangiopathy)
- Platelet-based problem
- Tiny clots form in small vessels
- Made of platelets + vWF
- Examples: TTP, HUS
- Causes: ADAMTS13 deficiency, Shiga toxin
vs
MAHA (Microangiopathic Hemolytic Anemia)
- RBC-based consequence
- RBCs sheared by fibrin strands in small vessels
- Result: schistocytes on smear
- All TMA can cause MAHA
- But MAHA also from prosthetic valves, DIC
The relationship: TMA is the cause (clots in small vessels). MAHA is the effect (RBCs get shredded passing through). All TMA produces MAHA, but not all MAHA comes from TMA · mechanical heart valves can shred RBCs too.
Board Trap · Heparin-Induced Thrombocytopenia
HIT-2 is the dangerous one. Here's the chain:
Heparin binds Platelet Factor 4 (PF4) → forms a complex → body makes IgG antibodies against it → these antibodies activate platelets → platelets consumed (count drops) BUT paradoxically cause thrombosis (both arterial AND venous).
Timeline: Days 3,10 after starting heparin. The trap: a patient on heparin whose platelet count drops · you might think "bleeding risk" but HIT actually causes clotting.
Action: Stop ALL heparin immediately. Switch to a direct thrombin inhibitor (argatroban, bivalirudin). NEVER give warfarin first (causes skin necrosis).
Prostaglandin Quick Reference
These come up in pharmacology constantly. Know what each one does.
| Prostaglandin | Platelet Effect | Vascular Effect | Other |
|---|---|---|---|
| Prostacyclin (PGI2) | Inhibits aggregation | Vasodilation | Opposes TXA2. Made by endothelium. |
| PGE2 | , | Vasodilation | Fever, inflammation, pain. Decreases gastric acid, increases mucus (protective). |
| PGF2α | , | Vasoconstriction | Bronchoconstriction. Uterine contraction (used to induce labor). |
| TXA2 | Promotes aggregation | Vasoconstriction | Made by platelets. Target of aspirin. |
The balance: Endothelium makes PGI2 (stop clotting). Platelets make TXA2 (promote clotting). Low-dose aspirin tips the balance toward PGI2 because platelets can't make new COX (they have no nucleus), but endothelial cells can.
Anti-Platelet Drugs
Four drug classes, four different mechanisms. Eliminate the wrong drugs to find the right class.
A patient with a coronary stent needs dual antiplatelet therapy. The cardiologist prescribes aspirin plus a drug that blocks the P2Y12 ADP receptor. Which drug class?
PDE inhibitor
ADP receptor blocker
GpIIb/IIIa inhibitor
COX inhibitor
A patient with peripheral artery disease and intermittent claudication needs a drug that inhibits phosphodiesterase to prevent platelet aggregation AND improve blood flow. Which drug?
Abciximab
Cilostazol
Clopidogrel
Ticagrelor
During a PCI procedure, the interventional cardiologist wants an IV drug that directly blocks fibrinogen from binding to the platelet surface. Which class?
Aspirin
ADP blocker
GpIIb/IIIa inhibitor
Dipyridamole
ADP Receptor Blockers
Drugs: Clopidogrel, ticlopidine, ticagrelor, prasugrel
Target: P2Y12 receptor
Toxicity: Ticlopidine = agranulocytosis. Clopidogrel = TTP (rare).
Use: Post-stent, ACS, stroke prevention
Target: P2Y12 receptor
Toxicity: Ticlopidine = agranulocytosis. Clopidogrel = TTP (rare).
Use: Post-stent, ACS, stroke prevention
tap for details
PDE Inhibitors
Drugs: Cilostazol, dipyridamole
Mechanism: Block cAMP breakdown → less TXA2, more prostacyclin
Use: Cilostazol for claudication, dipyridamole for stroke prevention (with aspirin)
Mechanism: Block cAMP breakdown → less TXA2, more prostacyclin
Use: Cilostazol for claudication, dipyridamole for stroke prevention (with aspirin)
tap for details
GpIIb/IIIa Inhibitors
Drugs: Abciximab, eptifibatide, tirofiban
Mechanism: Block fibrinogen binding to GpIIb/IIIa
Route: IV only (hospital setting)
Use: Acute coronary syndrome, PCI
Mechanism: Block fibrinogen binding to GpIIb/IIIa
Route: IV only (hospital setting)
Use: Acute coronary syndrome, PCI
tap for details
Aspirin
Mechanism: Irreversible COX inhibitor → blocks TXA2
Duration: Lasts platelet's entire life (8,10 days · no nucleus = can't make new COX)
Key: Anti-PLATELET, not anticoagulant. Does NOT affect PT or PTT.
Duration: Lasts platelet's entire life (8,10 days · no nucleus = can't make new COX)
Key: Anti-PLATELET, not anticoagulant. Does NOT affect PT or PTT.
tap for details
Aspirin Overdose: The Progression
Aspirin overdose is a board favorite because the acid-base changes are predictable and testable.
Early (Hours 1,6)
Salicylates directly stimulate the medullary respiratory center → hyperventilation → blow off CO2 → respiratory alkalosis. Tinnitus, nausea, vomiting.
Transition
Salicylates uncouple oxidative phosphorylation in mitochondria → cells can't make ATP efficiently → generate heat (hyperthermia) and switch to anaerobic metabolism → lactic acid builds up.
Late
Mixed respiratory alkalosis + metabolic acidosis with anion gap. The lungs are still hyperventilating (resp alk persists) but now organic acids are piling up (met acid). ABG: low CO2, low bicarb, elevated anion gap.
Severe / Terminal
Respiratory fatigue → CO2 retention → pure metabolic acidosis. CNS depression, seizures, coma. Treatment: alkalinize the urine (sodium bicarb) to trap salicylates in the kidney. Dialysis if severe.
Board Trap
Don't confuse aspirin's anti-platelet effect with an anticoagulant effect. Aspirin does NOT affect PT or PTT. It only affects bleeding time. If a question asks about aspirin and mentions PT/PTT · it's a distractor.
NSAID Quick Reference
NSAIDs are reversible COX inhibitors. They decrease PGE2 (pain, inflammation, fever, gastric protection). Unlike aspirin, they have no significant anti-platelet effect.
| Drug | High-Yield Fact | Board Clue |
|---|---|---|
| Ibuprofen | Most common OTC NSAID | "Over-the-counter pain reliever" |
| Indomethacin | Closes PDA (prostaglandin-dependent) | Premature infant with PDA; also acute gout |
| Naproxen | First-line for dysmenorrhea | "Painful periods" + NSAID choice |
| Ketorolac | Morphine-equivalent analgesic strength (IV/IM) | Post-surgical pain, renal colic; "NSAID as strong as opioid" |
COX-2 selective inhibitors (celecoxib): Spare COX-1 (stomach protection) but increase cardiovascular risk. Board pearl: patient with arthritis + history of GI bleed → COX-2 inhibitor might seem like the answer, but watch for CV history.
Villain Cards: Platelet Criminals
Tap each card to flip and reveal their mechanism, labs, and the one thing that separates them on the board.
ITP
Immune Assassin
tap to flip
ITP
WeaponIgG vs platelet surface antigens, splenic destruction
LabsIsolated low plt. PT/PTT normal. No schistocytes.
Kids vs AdultsKids: 90% self-resolve. Adults: 90% chronic.
TrapNever transfuse (antibodies destroy new platelets faster)
TxSteroids first. IVIG if urgent. Splenectomy if refractory.
TTP
Microthrombus Architect
tap to flip
TTP
Root causeADAMTS13 deficiency: giant vWF multimers form microthrombi
PentadPlt low, MAHA, Renal fail, Neuro sx, Fever
SmearSchistocytes (helmet cells). High LDH.
TxPlasmapheresis. NO platelet transfusion ever.
Trapvs ITP: both low plt, but TTP has schistocytes + multi-organ sx
HUS
Kidney Destroyer
tap to flip
HUS
TriggerE. coli O157:H7 Shiga toxin after bloody diarrhea (children)
TargetRenal microvasculature (AKI predominates)
vs TTPHUS = renal only. TTP = renal + neuro + fever + adult.
SmearSchistocytes. ADAMTS13 normal.
TrapNo antibiotics (worsen Shiga toxin release)
HIT
Paradox Clotter
tap to flip
HIT-2
WeaponIgG vs heparin-PF4 complex activates platelets
TimingDays 3-10 after heparin start
ParadoxLow platelets BUT causes arterial + venous THROMBOSIS
ActionStop all heparin. Switch to argatroban or bivalirudin.
TrapNever give warfarin first: protein C drops first, skin necrosis
DIC
The Everything Consumer
tap to flip
DIC
Trace ItMassive activation: burns through platelets AND coag factors
TriggersSepsis, obstetric emergency, malignancy, trauma
LabsLow plt + elevated PT/PTT + low fibrinogen + high D-dimer
SmearSchistocytes
TxTreat underlying cause. Replace: FFP + cryoprecipitate.
Decision Tree: Platelet Physiology: Primary vs Secondary Hemostasis
Tap a path to trace what happens at an injury site. Reset to explore the other branch.
A bleeding patient has normal PT and PTT but prolonged bleeding time. Which branch should you challenge first?
Not first. Factor cascade problems usually move PT, PTT, or both. Normal PT and PTT points away from coagulation factors.
Yes. Prolonged bleeding time with normal PT and PTT means the clotting factors are working, so test platelet number, adhesion, activation, aggregation, or vWF.
Ristocetin fails. What should you force yourself to separate before revealing the answer?
Yes. If normal plasma corrects the ristocetin problem, the missing piece was vWF. If normal plasma does not correct it and platelets are giant, the platelet receptor GpIb is missing.
No. PT and PTT sort coagulation pathways. Ristocetin sorts the vWF to GpIb adhesion handshake.
Site of injury: vessel wall breaks. What happens first?
Clinical Images
Real findings from the board. Tap any image to expand.
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Test Yourself
5 questions, shuffled from a larger pool. No timer. Wrong answers teach you something.
Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last updated July 5, 2026 at 8:17 PM ET
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