Coagulation Disorders & Bleeding Diathesis

A bleeding diathesis is an abnormal tendency to bleed, arising from defects in vessels, platelets, or coagulation factors (or excess fibrinolysis). This is one of the highest-yield Pathology clusters in NEET PG — the single most-tested skill being PT/aPTT pattern recognition. Master the cascade, the screening tests, and the classic disease-specific signatures, and you will rarely miss a question here.

Classification of bleeding disorders

Bleeding disorders are first split by the dominant compartment involved. This single distinction (platelet/vascular vs coagulation) drives the whole differential.

Feature	Platelet / vascular defect	Coagulation factor defect
Site of bleeding	Skin & mucous membranes	Deep tissues, joints, muscles
Lesion type	Petechiae, purpura, ecchymoses	Haematomas, haemarthrosis
Bleeding after cuts	Immediate, prolonged	Delayed (after hours)
Bleeding after surgery	Immediate	Delayed, prolonged
Sex predilection	Female > male	Male (X-linked haemophilias)
Prototype	ITP, von Willebrand disease	Haemophilia A/B

High-yield: Mucocutaneous bleeding (epistaxis, gum bleed, menorrhagia, petechiae) → think platelet/vWF problem. Deep bleeds into joints and muscles → think clotting factor (haemophilia).

A second axis is inherited vs acquired. Inherited: haemophilia A/B, von Willebrand disease (vWD), rare factor deficiencies. Acquired (commoner overall): DIC, liver disease, vitamin K deficiency, drug-induced (warfarin, heparin), immune thrombocytopenia.

The coagulation cascade

The classical cascade is divided into three arms. Although in vivo coagulation is really driven by the tissue factor (extrinsic) pathway with amplification, the in vitro model still governs lab interpretation.

• Intrinsic pathway (measured by aPTT): XII → XI → IX → VIII. Triggered in vitro by contact with negatively charged surfaces (kaolin, glass).
• Extrinsic pathway (measured by PT): Tissue factor (III) + VII. The shortest pathway; the physiological initiator in vivo.
• Common pathway: X → V → II (prothrombin → thrombin) → I (fibrinogen → fibrin), stabilised by factor XIII (cross-linking).

Stepwise initiation in vivo: Vascular injury → tissue factor exposed → TF–VIIa complex → activates X (and IX) → Xa + Va (prothrombinase) → thrombin → fibrin → XIIIa cross-links clot.

Mnemonic for vitamin K–dependent factors: "1972" → factors II, VII, IX, X (plus anticoagulant proteins C and S). These need gamma-carboxylation by vitamin K–dependent carboxylase.

High-yield: Factor VII has the shortest half-life (~4–6 h) among coagulation factors → PT prolongs first in early warfarin therapy, liver disease, and vitamin K deficiency.

High-yield: Factor VIII is the only coagulation factor NOT synthesised solely in the liver — it is also made by sinusoidal endothelial cells. Hence VIII can be normal or raised in liver disease while other factors fall. Factor VIII is also an acute-phase reactant.

Why factor XII deficiency does NOT cause bleeding

Factor XII (Hageman factor) deficiency prolongs aPTT markedly but causes NO clinical bleeding — a classic trap. The same is true for prekallikrein and HMWK deficiency. In vivo, the TF pathway bypasses contact activation.

Interpreting PT and aPTT — the core skill

This is the table to memorise cold.

Test	Pathway	Factors assessed	Drug monitored	Normal range
PT / INR	Extrinsic + common	VII, X, V, II, fibrinogen	Warfarin	PT 11–14 s; INR 0.9–1.2
aPTT	Intrinsic + common	XII, XI, IX, VIII, X, V, II, fibrinogen	Heparin (UFH)	25–40 s
Thrombin time	Fibrinogen → fibrin	Fibrinogen, thrombin inhibitors	—	14–16 s
Bleeding time	Platelet–vessel	Platelet number/function, vWF	—	2–7 min

Pattern recognition (the exam favourite)

PT	aPTT	Likely defect
Normal	Prolonged	Intrinsic only: VIII (haemophilia A), IX (B), XI, XII, vWD, heparin
Prolonged	Normal	Extrinsic only: Factor VII deficiency
Prolonged	Prolonged	Common pathway (X, V, II, fibrinogen), DIC, liver disease, warfarin overdose, vitamin K deficiency, heparin overdose
Normal	Normal	Factor XIII deficiency, mild platelet defect, vascular cause, mild vWD

Stepwise approach to a prolonged value: Prolonged test → repeat → do a MIXING STUDY (patient plasma + normal plasma 1:1).

1. Corrects → factor deficiency (the normal plasma supplies the missing factor).
2. Fails to correct → inhibitor present (e.g., lupus anticoagulant, factor VIII inhibitor/acquired haemophilia).

High-yield: Isolated prolonged PT with normal aPTT = factor VII deficiency (the only factor unique to the extrinsic limb). Isolated prolonged aPTT that does not correct on mixing = inhibitor, often lupus anticoagulant (paradoxically thrombotic, not bleeding).

High-yield: Factor XIII deficiency gives normal PT, aPTT, BT and platelet count. Diagnosis is via urea clot solubility test (clot dissolves in 5M urea). Classic features: delayed umbilical stump bleeding and poor wound healing.

Haemophilia A and B

X-linked recessive disorders of the intrinsic pathway. Males affected, females carriers (rare symptomatic carriers via lyonisation).

Feature	Haemophilia A	Haemophilia B (Christmas disease)
Deficient factor	VIII	IX
Frequency	~80–85% (commoner)	~15%
Inheritance	X-linked recessive	X-linked recessive
PT	Normal	Normal
aPTT	Prolonged	Prolonged
Platelets / BT	Normal	Normal
Treatment	Recombinant factor VIII; desmopressin (mild)	Recombinant factor IX

Severity correlates with residual factor level: Severe <1% (spontaneous haemarthrosis), moderate 1–5%, mild >5–40% (bleeds with trauma/surgery only).

Clinical hallmark: haemarthrosis (knees, ankles, elbows) → recurrent bleeds → target joints → haemophilic arthropathy. Also deep muscle haematomas (iliopsoas), prolonged post-surgical/post-dental bleeding.

High-yield: Desmopressin (DDAVP) raises factor VIII and vWF by releasing endothelial stores — useful in mild haemophilia A and type 1 vWD. It is useless in haemophilia B (does not raise factor IX).

High-yield: The most feared complication of replacement therapy is development of factor VIII inhibitors (alloantibodies) — suspect when a previously responsive patient stops responding and aPTT fails to correct on mixing. Managed with bypassing agents (activated PCC, recombinant factor VIIa) or emicizumab (factor VIII–mimetic bispecific antibody) for prophylaxis.

Von Willebrand disease (vWD)

The commonest inherited bleeding disorder (most are autosomal dominant, type 1). vWF has two jobs: (1) platelet adhesion to subendothelium (bridges GpIb to collagen) and (2) carrier/stabiliser of factor VIII. So vWD produces a combined platelet-type and mild coagulation-type picture.

Type	Defect	Notes
Type 1	Partial quantitative ↓	Commonest (~70%), mildest, AD
Type 2	Qualitative (2A, 2B, 2M, 2N)	2B → enhanced GpIb binding, may cause thrombocytopenia
Type 3	Near-total absence	Severe, autosomal recessive, very low VIII

Labs: prolonged BT, normal/prolonged aPTT (if VIII low), normal PT, normal platelet count (except 2B). Confirmatory: ↓ ristocetin cofactor activity and abnormal ristocetin-induced platelet aggregation (RIPA).

High-yield: Ristocetin cofactor assay is the functional test for vWF. In type 2B, RIPA is increased at low-dose ristocetin. Treatment: DDAVP for type 1; vWF-containing factor VIII concentrate for type 3 and type 2B (avoid DDAVP in 2B — can worsen thrombocytopenia).

Disseminated intravascular coagulation (DIC)

A consummative coagulopathy: widespread tissue factor release → systemic microthrombi → consumption of platelets and clotting factors → secondary fibrinolysis → bleeding. It is always secondary to an underlying trigger.

Triggers — mnemonic "STOP Making New Thrombi": Sepsis (gram-negative is classic), Trauma/burns, Obstetric (abruptio, amniotic fluid embolism, retained dead fetus, pre-eclampsia), Pancreatitis, Malignancy (acute promyelocytic leukaemia, adenocarcinomas — mucin), Neoplasm/snakebite, Transfusion reactions.

Laboratory signature of DIC:

Test	DIC result
Platelets	Low
PT	Prolonged
aPTT	Prolonged
Fibrinogen	Low (consumed)
D-dimer / FDPs	Markedly raised
Peripheral smear	Schistocytes (MAHA)

Flow: Trigger → thrombin generated → microvascular fibrin thrombi + ischaemia → platelets & factors consumed → plasmin activated → FDP/D-dimer ↑ → bleeding + organ failure.

High-yield: The most sensitive test for DIC is D-dimer (raised); the most useful single marker of severity/consumption is falling fibrinogen. Acute DIC bleeds; chronic DIC (e.g., adenocarcinoma, Trousseau syndrome) may present with thrombosis.

High-yield: Treat the underlying cause first. Supportive: FFP, cryoprecipitate (for fibrinogen), platelets. Acute promyelocytic leukaemia (APML, t(15;17)) classically presents with DIC — treat with ATRA which corrects the coagulopathy.

Thrombocytopenia and platelet disorders

Thrombocytopenia = platelet count <1,50,000/µL. Spontaneous bleeding risk rises below ~20,000; surgical risk below ~50,000.

Mechanisms

• ↓ Production: aplastic anaemia, leukaemia, marrow infiltration, B12/folate deficiency, drugs.
• ↑ Destruction: ITP, TTP/HUS, DIC, heparin-induced thrombocytopenia (HIT), hypersplenism (sequestration).

Immune thrombocytopenic purpura (ITP)

Autoantibodies (anti-GpIIb/IIIa) opsonise platelets → splenic destruction. Acute ITP: children, post-viral, self-limiting. Chronic ITP: adult women, may be associated with SLE, HIV, H. pylori.

• Labs: isolated thrombocytopenia, normal PT/aPTT, normal smear except low platelets (large/young platelets). Marrow shows increased megakaryocytes.
• Treatment: corticosteroids first line; IVIG (rapid rise, e.g., before surgery/bleeding); splenectomy for refractory; TPO-receptor agonists (eltrombopag, romiplostim); rituximab.

High-yield: ITP is a diagnosis of exclusion with isolated low platelets and normal coagulation profile. Bone marrow shows abundant megakaryocytes.

Thrombotic thrombocytopenic purpura (TTP)

Deficiency or inhibition of ADAMTS13 (the vWF-cleaving metalloprotease) → ultra-large vWF multimers → platelet microthrombi → microangiopathic haemolytic anaemia (MAHA).

Pentad — mnemonic "FAT RN": Fever, Anaemia (MAHA, schistocytes), Thrombocytopenia, Renal dysfunction, Neurological signs. (Neurological involvement dominates in TTP; renal dominates in HUS.)

High-yield: TTP = ↓ ADAMTS13. Treatment is urgent plasma exchange (plasmapheresis) — platelet transfusion is contraindicated (fuels thrombosis), unlike in ITP. Add caplacizumab/steroids in acquired TTP.

ITP vs TTP vs DIC — the must-know comparison

Feature	ITP	TTP	DIC
Platelets	Low	Low	Low
PT / aPTT	Normal	Normal	Prolonged
Schistocytes (MAHA)	No	Yes	Yes
Fibrinogen / D-dimer	Normal	Normal	↓ fibrinogen, ↑↑ D-dimer
Key mechanism	Anti-GpIIb/IIIa Ab	↓ ADAMTS13	Tissue factor, consumption
Treatment	Steroids/IVIG	Plasma exchange	Treat cause + FFP/cryo

High-yield: Normal PT/aPTT distinguishes ITP and TTP from DIC. Presence of schistocytes separates TTP from ITP.

Heparin-induced thrombocytopenia (HIT)

IgG against PF4–heparin complex → platelet activation → thrombosis despite thrombocytopenia, typically 5–10 days after starting heparin (~50% drop in platelets). Stop heparin; use a non-heparin anticoagulant (argatroban, fondaparinux, bivalirudin) — warfarin alone is dangerous (skin necrosis).

Inherited platelet function defects (normal count, prolonged BT)

• Glanzmann thrombasthenia: GpIIb/IIIa defect → impaired aggregation (aggregation absent with ADP/collagen but normal with ristocetin).
• Bernard–Soulier syndrome: GpIb defect → impaired adhesion → giant platelets, absent ristocetin aggregation.

Vitamin K deficiency & liver disease

• Vitamin K deficiency: ↓ functional II, VII, IX, X (and proteins C, S). PT prolongs first (factor VII), then aPTT. Causes: newborn (haemorrhagic disease of the newborn — prevent with IM vitamin K at birth), malabsorption, prolonged antibiotics, warfarin. Corrects with vitamin K.
• Liver disease: ↓ synthesis of all factors except VIII (and vWF). PT is a sensitive marker of synthetic function. Does NOT correct fully with vitamin K (synthetic failure, not just carboxylation).

High-yield: Vitamin K deficiency → corrects with vitamin K; liver disease → factor VIII normal/high and incomplete correction. This pair is a frequent distractor set.

Recently asked / exam angle

• PT/aPTT grids: "Isolated prolonged PT" → factor VII; "isolated prolonged aPTT, no bleeding" → factor XII; "both prolonged + low platelets + high D-dimer" → DIC.
• Mixing study correction vs non-correction → deficiency vs inhibitor (lupus anticoagulant).
• Normal PT/aPTT/BT/platelets but neonatal umbilical bleeding → factor XIII (urea clot solubility test).
• Ristocetin questions: decreased aggregation corrected by normal plasma → vWD; not corrected → Bernard–Soulier; absent with ADP but normal ristocetin → Glanzmann.
• Platelet transfusion contraindicated → TTP and HIT.
• DDAVP useless in haemophilia B; APML presents with DIC, treated by ATRA.
• Vitamin K–dependent factors (II, VII, IX, X, protein C & S) and factor with shortest half-life (VII).

Rapid revision

1. Mucocutaneous bleed = platelet/vWF; deep/joint bleed = coagulation factor.
2. PT monitors warfarin (extrinsic, factor VII); aPTT monitors heparin (intrinsic).
3. Isolated ↑PT = factor VII deficiency; isolated ↑aPTT without bleeding = factor XII.
4. Mixing study corrects → deficiency; fails → inhibitor (lupus anticoagulant).
5. Vitamin K–dependent: II, VII, IX, X + protein C & S ("1972"); shortest t½ = VII.
6. Haemophilia A (VIII) > B (IX), both X-linked, ↑aPTT, normal PT; haemarthrosis.
7. DDAVP helps mild haemophilia A and type 1 vWD; useless in haemophilia B.
8. vWD = commonest inherited bleeding disorder; ristocetin cofactor assay confirms.
9. DIC = ↓platelets, ↑PT, ↑aPTT, ↓fibrinogen, ↑↑D-dimer, schistocytes.
10. TTP = ↓ADAMTS13, pentad "FAT RN", treat with plasma exchange; never give platelets.
11. ITP = anti-GpIIb/IIIa, isolated thrombocytopenia, normal coagulation, ↑megakaryocytes; steroids/IVIG.
12. Factor XIII deficiency = normal all screens, delayed umbilical bleed, urea clot solubility test; Bernard–Soulier = giant platelets + absent ristocetin aggregation; Glanzmann = GpIIb/IIIa defect.