Platelet Function and Primary Haemostasis
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Direct answer
Platelets are anucleate cytoplasmic fragments shed from megakaryocytes that run primary haemostasis in three linked steps: adhesion to injured endothelium through von Willebrand factor binding glycoprotein Ib, activation with granule release and thromboxane A2 synthesis, and aggregation as activated glycoprotein IIb/IIIa receptors bridge platelets with fibrinogen. A plug forms within seconds, and the coagulation cascade then stabilises it with fibrin — which is why platelet disorders bleed into skin and mucosae (petechiae) while coagulation disorders bleed into joints and soft tissue.
What you must remember
- Normal count 150,000–450,000 per microlitre; lifespan 8–10 days; about one-third pooled in the spleen.
- Thrombopoietin comes constitutively from the liver and is cleared by platelets themselves — a feedback that raises thrombopoietin when platelets fall, as in ITP.
- Adhesion: collagen binds vWF, vWF binds GPIb — defective in Bernard-Soulier syndrome (giant platelets, absent GPIb).
- Activation: shape change, calcium rise, dense-granule ADP release, and thromboxane A2 generation via cyclooxygenase-1 from arachidonic acid.
- Aggregation: GPIIb/IIIa conformational change lets fibrinogen bridge adjacent platelets — defective in Glanzmann thrombasthenia (normal count, no clumping).
- Aspirin irreversibly acetylates COX-1 for the platelet's remaining lifespan (stop about 7 days before surgery); clopidogrel blocks the P2Y12 ADP receptor; abciximab blocks GPIIb/IIIa.
- Bleeding time (Ivy method 2–7 minutes) tests primary haemostasis; it prolongs below about 100,000 platelets, in uraemia (acquired granule dysfunction) and in von Willebrand disease, while coagulation screens stay normal.
- Serious spontaneous bleeding typically appears below 20,000 per microlitre — petechiae, gum oozing, menorrhagia.
A cut on the finger, second by second
Watch the physiology unfold in real time. The transected vessel constricts immediately — local myogenic reflex plus platelet serotonin and thromboxane — slowing flow so platelets can catch the injury. Exposed subendothelial collagen grabs vWF, which changes shape under shear and clamps onto platelet GPIb: this is adhesion, and it fails in Bernard-Soulier syndrome. The tethered platelet activates within a second: it spreads, pours out ADP from dense granules, makes thromboxane A2, and recruits neighbours — this is activation, and it is the step aspirin abolishes. Finally, GPIIb/IIIa receptors flip open and fibrinogen staples platelet to platelet: aggregation, the step that fails in Glanzmann thrombasthenia, where the plug never forms despite normal numbers.
The plug alone would wash away, so tissue factor activates the coagulation cascade and fibrin strands weave through it; then prostacyclin and nitric oxide from neighbouring intact endothelium confine the clot to the wound edge. This chain explains drug effects at the bedside: aspirin lengthens bleeding time but changes neither PT nor aPTT, because it touches primary haemostasis only. In uraemia, retained toxins quench granule release and NO overproduction paralyses adhesion, which is why renal-failure patients ooze despite normal counts — desmopressin helps by releasing endothelial vWF.
Distinguishing the two classic platelet defects
Bernard-Soulier syndrome and Glanzmann thrombasthenia appear in every exam as a matched pair, and the discriminator is mechanistic, not mnemonic. Bernard-Soulier lacks GPIb, so platelets cannot stick to vWF on collagen — adhesion failure, and the smear shows giant platelets because the cytoskeletal defect of the membrane interferes with fragmentation from megakaryocytes. Glanzmann lacks GPIIb/IIIa, so platelets stick but cannot bind fibrinogen to each other — aggregation failure with normal-sized platelets. Both give lifelong mucocutaneous bleeding with a prolonged bleeding time and normal PT/aPTT, and both are autosomal recessive. Ristocetin summarises the difference in one test: it induces vWF-mediated agglutination, which fails in Bernard-Soulier and succeeds in Glanzmann — a favourite viva endpoint.
Frequently asked questions
Which glycoprotein receptor mediates platelet adhesion?
Glycoprotein Ib binds von Willebrand factor attached to subendothelial collagen; its congenital absence causes Bernard-Soulier syndrome.
How does aspirin affect platelet function?
It irreversibly acetylates cyclooxygenase-1, abolishing thromboxane A2 synthesis for the platelet's 8–10 day lifespan, so antiplatelet effect persists until new platelets arrive.
What is tested by the Ivy bleeding time?
Primary haemostasis — platelet number and function plus vessel contraction; it is prolonged in thrombocytopenia, uraemia and von Willebrand disease but not in haemophilia.
Why do platelet disorders cause petechiae while coagulation disorders cause haematomas?
Superficial capillary leaks need platelet plugs immediately, so their failure gives pinpoint skin and mucosal bleeds; deeper vessels rely on fibrin clot stability, so factor deficiencies bleed into muscles and joints.
What happens to megakaryocytes in immune thrombocytopenic purpura?
They increase in number and size because thrombopoietin rises as peripheral platelets are destroyed by anti-GPIIb/IIIa antibodies, so the marrow shows a compensatory response.