Haemostasis & Blood Transfusion

Haemostasis is the physiological arrest of bleeding through an integrated response of blood vessels, platelets and coagulation factors. For NEET PG this topic spans the coagulation cascade, inherited and acquired coagulopathies, massive transfusion protocols and the entire spectrum of transfusion reactions — all heavily examined in trauma and perioperative surgical vignettes.

Normal Haemostasis — The Four Phases

Haemostasis proceeds in an orderly, overlapping sequence. Remembering the phases lets you slot any clinical bleeding problem into the correct mechanism.

1. Vascular phase — immediate reflex vasoconstriction (mediated by endothelin, thromboxane A2, serotonin) reduces blood flow.
2. Platelet phase (primary haemostasis) — platelets adhere to exposed subendothelial collagen via von Willebrand factor (vWF) binding to GpIb, then aggregate via GpIIb/IIIa crosslinked by fibrinogen, forming the soft platelet plug.
3. Coagulation phase (secondary haemostasis) — the cascade generates thrombin, which converts fibrinogen to fibrin, stabilising the plug.
4. Fibrinolysis — plasmin (from plasminogen, activated by tPA) degrades fibrin once healing is underway, producing fibrin degradation products (FDPs) and D-dimer.

Endothelial injury → vasoconstriction → platelet adhesion (vWF–GpIb) → activation & aggregation (GpIIb/IIIa–fibrinogen) → coagulation cascade → fibrin clot → fibrinolysis & remodelling.

High-yield: Primary haemostasis defects (platelet/vWF problems) cause immediate mucocutaneous bleeding — petechiae, epistaxis, menorrhagia. Secondary haemostasis defects (clotting factor problems) cause delayed, deep bleeding — haemarthroses, muscle haematomas, rebleeding after surgery.

The Coagulation Cascade

Classically divided into intrinsic, extrinsic and common pathways. In vivo, the tissue factor (extrinsic) pathway is the principal initiator; the intrinsic pathway amplifies the response.

Pathway	Trigger	Key factors	Lab test
Extrinsic	Tissue factor (factor III)	VII	PT / INR
Intrinsic	Contact activation (collagen, kallikrein)	XII, XI, IX, VIII	aPTT
Common	Convergence	X, V, II (prothrombin), I (fibrinogen), XIII	PT + aPTT

• Vitamin K-dependent factors: II, VII, IX, X (plus proteins C and S). Mnemonic: "1972" (factors 10, 9, 7, 2). Vitamin K is needed for gamma-carboxylation; warfarin blocks vitamin K epoxide reductase.
• Factor VII has the shortest half-life (4–6 h) → PT/INR rises first with warfarin and in early liver disease.
• Factor XIII crosslinks fibrin; deficiency gives normal PT/aPTT but poor clot stability and delayed umbilical-stump bleeding.

High-yield: Both PT and aPTT prolonged with a normal platelet count points to a common-pathway factor deficiency, DIC, liver disease, or supratherapeutic anticoagulation. Isolated aPTT prolongation = intrinsic (think haemophilia A/B, factor XII, heparin). Isolated PT prolongation = extrinsic (factor VII, early warfarin/liver disease).

Inherited Coagulopathies

Haemophilia

X-linked recessive; affects males, carried by females.

Feature	Haemophilia A	Haemophilia B	von Willebrand disease
Deficiency	Factor VIII	Factor IX	vWF (± low VIII)
Inheritance	X-linked recessive	X-linked recessive	Autosomal dominant (mostly)
Bleeding type	Deep (haemarthrosis)	Deep (haemarthrosis)	Mucocutaneous
aPTT	Prolonged	Prolonged	Prolonged or normal
PT	Normal	Normal	Normal
Bleeding time	Normal	Normal	Prolonged
Treatment	Recombinant factor VIII; desmopressin (mild)	Recombinant factor IX	Desmopressin; vWF/VIII concentrate

• Haemophilia B is also called Christmas disease.
• vWD is the most common inherited bleeding disorder overall (autosomal, affects both sexes).
• Desmopressin (DDAVP) releases vWF and VIII from endothelial Weibel–Palade bodies — useful in mild haemophilia A and type 1 vWD; ineffective/contraindicated in type 2B (causes thrombocytopenia) and type 3 vWD.

High-yield: A child with recurrent haemarthroses, prolonged aPTT, normal PT and normal platelet count → haemophilia A until proven otherwise. Confirm with factor VIII assay.

Acquired Coagulopathies

• Liver disease: decreased synthesis of all factors except VIII and vWF (made by endothelium). PT/INR is the most sensitive early marker.
• Vitamin K deficiency: prolonged PT then aPTT; seen in obstructive jaundice (no bile salts → no fat-soluble vitamin absorption), prolonged antibiotics, malabsorption, neonates (haemorrhagic disease of newborn).
• DIC (Disseminated Intravascular Coagulation): consumptive coagulopathy triggered by sepsis (most common), trauma, obstetric catastrophe (abruptio placentae, amniotic fluid embolism), malignancy, snake bite.

DIC parameter	Direction
Platelets	↓
PT / aPTT	↑ (prolonged)
Fibrinogen	↓
D-dimer / FDP	↑↑
Schistocytes on film	Present

High-yield: D-dimer and FDPs are raised with low fibrinogen and falling platelets in DIC — this combination is the classic exam quartet. Treat the underlying cause; supportive transfusion (FFP, cryoprecipitate, platelets) only if bleeding.

Lab Investigations of Haemostasis

Test	Measures	Normal range
Platelet count	Primary haemostasis	1.5–4 lakh/µL
Bleeding time	Platelet–vessel interaction	2–7 min
PT	Extrinsic + common	11–14 s
INR	Standardised PT	0.8–1.2
aPTT	Intrinsic + common	25–40 s
Thrombin time	Fibrinogen → fibrin	14–16 s
Fibrinogen	Clottable protein	200–400 mg/dL

• Mixing study: correction of prolonged aPTT after mixing with normal plasma → factor deficiency; no correction → inhibitor (e.g. lupus anticoagulant, factor VIII inhibitor).
• TEG/ROTEM (thromboelastography): point-of-care viscoelastic assay increasingly used in trauma and liver transplant to guide goal-directed transfusion — distinguishes factor deficiency, low fibrinogen, platelet dysfunction and hyperfibrinolysis in real time.

Blood Components & Their Indications

Whole blood is rarely used; component therapy is standard.

Component	Contents	Volume	Key indication
Packed red cells (PRBC)	RBCs, Hct ~70%	~250–300 mL	Symptomatic anaemia, acute blood loss
Fresh frozen plasma (FFP)	All clotting factors	~200–250 mL	Multiple factor deficiency, warfarin reversal (if no PCC), DIC, liver disease with bleeding
Cryoprecipitate	Fibrinogen, VIII, vWF, XIII, fibronectin	~15–20 mL	Hypofibrinogenaemia (<100 mg/dL), DIC, vWD/haemophilia A when concentrate unavailable
Platelet concentrate	Platelets	~50 mL	Thrombocytopenia with bleeding, prophylaxis

• 1 unit PRBC raises haemoglobin by ~1 g/dL (haematocrit ~3%) in an adult.
• 1 unit platelets (random donor) raises count by ~5,000–10,000/µL; a single-donor apheresis unit ≈ 6 RDP units.
• Cryoprecipitate is the richest concentrated source of fibrinogen — the answer when the stem says fibrinogen <100 mg/dL with bleeding.

High-yield: FFP is NOT a volume expander and should not be used solely to correct a mildly abnormal INR without bleeding or a planned procedure. For warfarin reversal with major bleeding, 4-factor prothrombin complex concentrate (PCC) plus IV vitamin K is preferred over FFP.

Transfusion thresholds

• Restrictive strategy (Hb 7 g/dL trigger) is preferred in most stable critically ill / GI bleed patients; transfuse to keep Hb 7–9 g/dL.
• Hb <8 g/dL threshold for cardiac patients / symptomatic.
• Platelet transfusion prophylactic threshold: <10,000/µL (stable), <20,000 with sepsis/fever, <50,000 before surgery or invasive procedure, <1,00,000 for neurosurgery/ophthalmic surgery.

Massive Haemorrhage / Massive Transfusion Protocol (MTP)

Massive transfusion is defined as ≥10 units of PRBC in 24 h, or replacement of one blood volume in 24 h, or ≥4 units in 1 h / loss of 50% blood volume in 3 h.

Modern trauma resuscitation uses balanced (1:1:1) ratio of PRBC : FFP : platelets to recreate whole blood and prevent dilutional coagulopathy.

Recognise major haemorrhage → activate MTP → 1:1:1 PRBC:FFP:platelets → give tranexamic acid early (<3 h) → keep warm, correct calcium, prevent acidosis → guide further therapy by TEG/ROTEM & labs.

• Tranexamic acid (TXA) — antifibrinolytic; CRASH-2 trial showed mortality benefit when given within 3 hours of trauma. Loading 1 g over 10 min, then 1 g over 8 h.
• Lethal triad of trauma: hypothermia + acidosis + coagulopathy (a vicious self-perpetuating cycle).

Complications of massive transfusion

Complication	Mechanism
Hypocalcaemia	Citrate chelates calcium
Hyperkalaemia	K⁺ leak from stored cells
Hypothermia	Cold stored blood
Metabolic alkalosis	Citrate → bicarbonate
Dilutional coagulopathy & thrombocytopenia	Factor/platelet-poor PRBC
2,3-DPG depletion	Left-shifted O₂ curve

High-yield: Citrate toxicity in massive transfusion causes hypocalcaemia (perioral tingling, tetany, prolonged QT) — treat with IV calcium gluconate. Citrate is the most-tested anticoagulant-additive complication.

Transfusion Reactions

A major exam favourite — match the timing and features to the reaction.

Reaction	Onset	Cause	Key features	Management
Acute haemolytic	Minutes	ABO incompatibility (clerical error)	Fever, loin pain, hypotension, haemoglobinuria, DIC	STOP transfusion, IV fluids, maintain urine output
Febrile non-haemolytic	1–6 h	Recipient antibodies vs donor WBC cytokines	Fever, chills, no haemolysis	Antipyretics; leucodepletion prevents
Allergic (urticarial)	Minutes–hours	Donor plasma proteins	Itching, hives	Antihistamines
Anaphylaxis	Minutes	IgA deficiency with anti-IgA	Bronchospasm, shock	Adrenaline; washed/IgA-deficient products
TACO	<6 h	Circulatory overload	Dyspnoea, hypertension, raised JVP, normal BNP↑	Diuretics, slow/stop transfusion
TRALI	<6 h	Anti-leucocyte antibodies → pulmonary oedema	Hypoxia, normal JVP/normotensive, bilateral infiltrates	Supportive, ventilation
Delayed haemolytic	5–14 days	Anamnestic antibody (Kidd, Rh)	Falling Hb, jaundice, positive DAT	Usually supportive
TA-GVHD	1–6 weeks	Donor lymphocytes attack host	Pancytopenia, rash, diarrhoea, high mortality	Prevent by irradiation of products

High-yield: Acute haemolytic transfusion reaction is almost always due to a clerical/identification error causing ABO incompatibility — the single most lethal transfusion error. The first step is always to STOP the transfusion and keep the IV line open with normal saline.

High-yield: TRALI vs TACO — both cause acute pulmonary oedema within 6 h. TACO has raised JVP, hypertension and responds to diuretics (volume overload); TRALI is normo-/hypotensive with normal JVP and is immune-mediated. TRALI is a leading cause of transfusion-related mortality.

Prevention measures

• Leucodepletion (leucoreduction): reduces febrile reactions, CMV transmission and HLA alloimmunisation.
• Irradiation: prevents TA-GVHD in immunocompromised / neonatal / directed-donation recipients.
• Washed cells: for IgA-deficient patients and recurrent severe allergic reactions.

Anticoagulants & Their Reversal

Drug	Action	Monitoring	Reversal
Heparin (UFH)	Activates antithrombin → inhibits IIa, Xa	aPTT	Protamine sulphate
LMWH (enoxaparin)	Mainly anti-Xa	Anti-Xa (usually none)	Partial protamine
Warfarin	Blocks vitamin K epoxide reductase	INR	Vitamin K, FFP, PCC
Dabigatran	Direct thrombin inhibitor	—	Idarucizumab
Rivaroxaban/apixaban	Direct factor Xa inhibitor	—	Andexanet alfa, PCC

• Protamine fully reverses unfractionated heparin but only partially reverses LMWH.
• Heparin-induced thrombocytopenia (HIT) — immune (type II), antibodies vs platelet factor 4–heparin complex, paradoxically prothrombotic; stop heparin, start a non-heparin anticoagulant (argatroban, fondaparinux). Suspect with a >50% platelet drop 5–10 days after starting heparin (the "4Ts" score).

Storage & Compatibility Facts

• CPDA-1 stored PRBC last 35 days; with additive solutions (SAGM) up to 42 days, at 2–6°C.
• Platelets stored at 20–24°C with agitation, shelf life 5 days (sepsis risk highest).
• FFP/cryoprecipitate stored frozen (−30°C, up to 1 year); must be transfused within hours of thawing.
• Universal donor: O negative (packed cells). Universal recipient: AB positive. Universal plasma donor: AB.
• Cross-match before transfusion; in extreme emergency give O-negative uncross-matched blood.

Key Differentials — Bleeding Patterns

• Petechiae + mucosal bleeding, normal PT/aPTT, low platelets → thrombocytopenia (ITP, DIC, marrow failure).
• Prolonged bleeding time, normal platelet count → platelet function defect or vWD.
• Isolated prolonged aPTT, corrects on mixing → haemophilia / factor deficiency; no correction → inhibitor / lupus anticoagulant.
• Prolonged PT + aPTT, low fibrinogen, high D-dimer → DIC.
• Prolonged PT first, then aPTT, history of jaundice/antibiotics → vitamin K deficiency.

Recently asked / exam angle

• A trauma patient receiving multiple units develops perioral tingling and a prolonged QT → citrate-induced hypocalcaemia (give calcium gluconate).
• Most common cause of a fatal transfusion reaction → ABO incompatibility from clerical error (acute haemolytic).
• Cryoprecipitate is the component of choice for hypofibrinogenaemia / factor XIII deficiency.
• Vitamin K-dependent factors mnemonic "1972" (10, 9, 7, 2) plus proteins C & S — recurrently asked.
• TXA in trauma must be given within 3 hours (CRASH-2) — frequently tested time cut-off.
• Differentiating TRALI (normal JVP, immune) from TACO (raised JVP, overload) is a perennial single-best-answer item.
• Distinguishing HIT type II (immune, prothrombotic, day 5–10) and the next step (stop heparin, start argatroban).
• Component to prevent TA-GVHD = irradiated blood; to prevent febrile reactions = leucodepleted blood.
• Reversal agent pairings: protamine–heparin, idarucizumab–dabigatran, andexanet–rivaroxaban.

Rapid revision

1. Vitamin K-dependent factors: II, VII, IX, X + protein C & S → "1972".
2. Factor VII has the shortest half-life → PT rises first.
3. PT/INR = extrinsic; aPTT = intrinsic; both prolonged = common pathway / DIC / liver disease.
4. vWD is the commonest inherited bleeding disorder; haemophilia A (factor VIII) the commonest severe one.
5. Primary haemostasis defect = immediate mucocutaneous bleed; secondary = delayed deep haemarthrosis.
6. Mixing study corrects → deficiency; doesn't correct → inhibitor.
7. DIC = ↓platelets, ↑PT/aPTT, ↓fibrinogen, ↑↑D-dimer, schistocytes.
8. 1 unit PRBC ↑ Hb by ~1 g/dL; 1 unit platelets ↑ count by ~5–10k.
9. Massive transfusion = ≥10 units/24 h; resuscitate 1:1:1 PRBC:FFP:platelets + TXA within 3 h.
10. Citrate toxicity → hypocalcaemia; stored blood → hyperkalaemia + hypothermia.
11. Acute haemolytic reaction = ABO clerical error → stop transfusion first, NS line open.
12. TRALI = normal JVP/normotensive; TACO = raised JVP → diuretics. Irradiate to prevent TA-GVHD; leucodeplete to prevent febrile reactions.