11.2 Hemostasis and Coagulation

11.2 Hemostasis and Coagulation

Quick Answer: Primary hemostasis is platelets plus vWF. Secondary hemostasis is the coagulation cascade. Vitamin K–dependent factors are II, VII, IX, X (and proteins C and S). Labile factors are V and VIII — that is why FFP is frozen within 8 hours. PT/INR watches the extrinsic path (VII); aPTT watches the intrinsic path (VIII, IX, XI, XII). Issue platelets for count or function, plasma for multiple-factor deficiency, cryo for fibrinogen/FXIII (and selected vWF), and a concentrate when a single factor is missing.

This is outline III.B.2. Chapter 4.2 told you what is in the bag and how long it lasts. This section is why that bag exists: name the lesion, name the assay, pick the product.

Primary versus secondary hemostasis

Vascular injury starts primary hemostasis. Exposed collagen and endothelial vWF recruit platelets. Platelets adhere through GPIb-IX-V binding vWF, then aggregate through GPIIb/IIIa binding fibrinogen. The plug stops capillary and mucosal bleeding — petechiae, epistaxis, immediate surgical oozing. Defects live here: thrombocytopenia, aspirin or uremic dysfunction, Glanzmann thrombasthenia (no GPIIb/IIIa), Bernard–Soulier (no GPIb), and von Willebrand disease.

Secondary hemostasis is fibrin that welds that plug. Tissue factor plus Factor VII starts the extrinsic path. Contact factors XII, XI, IX, and VIII are the intrinsic path. Both activate X, then V, II (prothrombin → thrombin), and I (fibrinogen → fibrin). Factor XIII covalently cross-links fibrin. Defects look like deep hematomas, hemarthroses, and delayed re-bleeding — hemophilia, vitamin K deficiency/warfarin, liver failure, DIC, FXIII deficiency.

The blood bank is not the coagulation bench, but BB items expect you to map the bleeding pattern to the component.

Factors you must be able to name

Vitamin K–dependent: II, VII, IX, X, plus regulatory protein C and protein S. Warfarin and nutritional vitamin K deficiency lower this set together. Factor VII has the shortest half-life (about 4–6 hours), so PT/INR prolongs first. Four-factor PCC (II, VII, IX, X) plus vitamin K is preferred for urgent warfarin reversal when available; FFP is the historical volume-heavy substitute.

Labile factors: V and VIII. They decay in liquid plasma at 1–6 °C. That is the physiologic reason FFP must be frozen within 8 hours and why PF24 has modestly lower VIII (Chapter 4.2). After thaw, VIII and V continue to fall, so thawed plasma through day 5 is not a dedicated Factor VIII dose. Hemophilia A is VIII; treat it with a concentrate, not generic FFP, when a concentrate exists. There is still no standalone U.S. Factor V concentrate — multiple-factor or isolated V deficiency that needs replacement is a plasma problem.

Fibrinogen (Factor I) is the substrate thrombin acts on. Critical hypofibrinogenemia in a bleeding adult is commonly treated at < 100–150 mg/dL (higher obstetric targets appear on some protocols). That is cryoprecipitate or fibrinogen concentrate, not a four-unit FFP gesture. Each conventional cryo unit is manufactured toward ≥ 150 mg fibrinogen.

Factor XIII cross-links fibrin. Deficiency is rare, PT and aPTT are normal, and bleeding is delayed. Replacement is FXIII concentrate, or cryo if concentrate is not available.

vWF is in plasma and is concentrated in cryo. Mild type 1 disease may respond to DDAVP. Significant type 2 or type 3 needs a vWF-containing concentrate. Cryo is a fallback, not first-line when a licensed concentrate is on the shelf.

PT, aPTT, thrombin time, mixing studies

PT/INR uses tissue-factor (thromboplastin) reagent. It is prolonged by VII and by common-path X, V, II, and fibrinogen, and by warfarin. An isolated long PT → think Factor VII first.

aPTT uses a contact activator. It is prolonged by XII, XI, IX, VIII, common-path factors, heparin, and many lupus anticoagulants. Isolated long aPTT plus bleeding → VIII, IX, or XI. Isolated long aPTT without bleeding → XII, prekallikrein/HMWK, or lupus anticoagulant. Do not issue plasma to “correct” a lupus anticoagulant that is not a bleeding diathesis.

Thrombin time (TT) adds thrombin to plasma. It is prolonged by low or dysfibrinogenemia, heparin, and fibrin(ogen) degradation products. Reptilase time is heparin-insensitive and splits heparin from a fibrinogen problem.

Mixing study: 1:1 patient plasma + normal plasma. Correction means factor deficiency. Failure to correct means inhibitor (specific factor inhibitor or lupus anticoagulant). Some Factor VIII inhibitors are time-dependent: the mix corrects immediately and prolongs after incubation. Incubate when the story is hemophilia with new poor recovery.

BB relevance: a panagglutinin on a panel is not a mixing study. If the clinical team wants “factors,” ask which assay is abnormal and whether the mix corrected before issuing four FFP.

Platelet disorders the outline expects

Thrombocytopenia is a count problem (ITP, marrow failure, consumption, dilution). Dysfunction is a function problem at a normal or near-normal count.

• Aspirin / many NSAIDs — COX-1 block, less thromboxane A2. Aspirin is irreversible for that platelet’s 8–10 day life. Platelet transfusion can supply unaffected platelets if bleeding is life-threatening; it is not an antidote you give for every aspirin tablet.
• Uremia — retained toxins impair adhesion and aggregation. First moves are dialysis and DDAVP, not reflexive platelets. Transfuse platelets if the patient is still bleeding through those measures.
• Glanzmann thrombasthenia — absent GPIIb/IIIa. Aggregation fails with all usual agonists except ristocetin. Patients can make anti-GPIIb/IIIa and become platelet-refractory.
• Bernard–Soulier — absent GPIb, giant platelets, no ristocetin aggregation. Same “function, not count” transfusion logic.

Do not diagnose these from a type-and-screen. Do recognize the name and pick platelet support plus hematology, not FFP.

Component choice

• Platelets — count below the institutional trigger (often 10 × 10^9/L prophylactically in a stable inpatient; higher for bleeding or an invasive procedure) or known dysfunction with bleeding.
• Plasma (FFP/PF24) — multiple-factor deficiency: bleeding liver failure, bleeding DIC, massive transfusion, TTP as the plasma-exchange replacement fluid (ADAMTS13), or emergency warfarin reversal when PCC is not available. A typical dose is about 10–20 mL/kg, not “two units for every adult.”
• Cryoprecipitate — fibrinogen, FXIII, and selected vWF/VIII when concentrates are not available. Cryo is not a warfarin-reversal product: it is the wrong factor set and the wrong volume of II/VII/IX/X.
• Concentrates preferred when available — PCC, fibrinogen concentrate, FVIII, FIX, FXIII, vWF, and labeled recombinant VIIa settings. Specific, virally safer, smaller volume.

Worked scenario. A bleeding patient on warfarin has INR 4.2, fibrinogen 280 mg/dL, and platelets 180 × 10^9/L. The missing set is vitamin K–dependent factors. PCC plus vitamin K is first-line. FFP is the substitute if PCC is not in house. Cryo will not fix the INR. Platelets will not fix the INR.

Exam traps. Labile = V and VIII, not the vitamin K set. PT is VII/extrinsic; aPTT is VIII/IX/XI/XII. A mix that does not correct is an inhibitor. Cryo is fibrinogen/FXIII/vWF, not PCC. Aspirin is a function problem for the life of that platelet. Factor XII does not get a product.