Bleeding Disorders · the physiology
Hemostasis as a four-beat process — START, MAKE, STOP, CLEAN — the foundation for classifying every bleeding disorder.
Hemostasis is a balance
Blood must stay fluid inside the vessel yet clot the instant one breaks. The hemostatic system is a scale — clot formation on one side, clot prevention on the other. Tip it either way and disease follows.
Clot formation
Coagulation · platelets · endothelium.
Too much → thrombophilia (hypercoagulable).
Clot prevention
Fibrinolysis · anticoagulation.
Too much → bleeding tendency (hypocoagulable).
An interrelated process
Hemostasis runs in four movements. Step through them.
START · endothelium + platelets
Vessel injury exposes collagen & tissue factor. Platelets adhere, activate, and aggregate into the primary platelet plug.
MAKE · coagulation cascade
On the platelet surface, the cascade generates thrombin, which converts fibrinogen to a fibrin clot that stabilises the plug.
STOP · natural anticoagulants
TFPI, protein C, protein S, and antithrombin switch the reaction off — confining the clot to the site of injury.
CLEAN · fibrinolysis
Plasmin digests the fibrin mesh into degradation products (including D-dimer), reopening the vessel once healing is done.
The platelet plug
Platelets do three things in sequence — adhere, aggregate, secrete — each through a specific glycoprotein receptor.
| Receptor | Binds | Action |
|---|---|---|
| GPIb | von Willebrand factor | Adhesion |
| GPIa-IIa | Collagen | Adhesion |
| GPVI | Collagen | Activation |
| GPIIb-IIIa | Fibrinogen | Aggregation |
Activated platelets secrete ADP, serotonin (→ vasoconstriction) and thromboxane A₂ (→ more aggregation), and expose phospholipid for the cascade.
The cascade: old vs new
The classic Y-shaped cascade explains the lab tests; the modern cell-based model explains what actually happens on the platelet. Toggle.
Initiation
TF + FVIIa on the injured cell make a small amount of thrombin — not enough.
Amplification
That thrombin loops back to activate FV, FVIII, FIX and platelets.
Propagation
A thrombin burst on the platelet surface → soluble fibrin → (FXIIIa) cross-linked, insoluble fibrin.
Same factors, but a loop — thrombin builds the very machine that makes more thrombin.
The numbers worth memorising
Vitamin-K factors
II, VII, IX, X (“1972”) — the warfarin targets.
Intrinsic (aPTT)
XII, XI, IX, VIII.
Common
X, V, II (prothrombin), I (fibrinogen).
Natural anticoagulants
The termination phase confines the clot to the wound.
TFPI
Blocks the TF–VIIa trigger.
Protein C
Inactivates Va & VIIIa.
Protein S
Cofactor for activated protein C.
Antithrombin
Inhibits thrombin & Xa (heparin’s target).
Fibrinolysis & the D-dimer
Once healed, plasmin dismantles the mesh — and the fragments it leaves become a clinical test.
Inhibitors keep it in check: PAI-1 blocks tPA; TAFI slows plasmin generation. A raised D-dimer signals that clot has formed and been broken down.
End of lecture — the foundation for the full Disorders of Hemostasis deck.
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