Acquired coagulation disorders

Pathology

Acquired coagulation disorders develop after birth secondary to systemic disease, drugs, or autoantibodies. They are more common than inherited disorders and often involve multiple factor deficiencies.

Key acquired coagulation disorders include:

Vitamin K deficiency
Liver disease associated coagulopathy
Disseminated intravascular coagulation (DIC)
Autoantibody inhibition of coagulation
Other miscellaneous causes e.g. transfusion syndrome

These are considered in more detail below:

Vitamin K deficiency

Causes:

Haemorrhagic disease of the newborn
Biliary obstruction (fat malabsorption)
Malnutrition/malabsorption (e.g. pancreatic, bowel disease)
Vitamin K antagonist therapy (warfarin)
Prolonged antibiotic use (↓ gut flora)

Pathophysiology:
Reduced activity of vitamin K–dependent factors (II, VII, IX, X, protein C, protein S)
Labs:

Prolonged PT (early)
Prolonged aPTT in severe cases
Normal platelet count

Clinical features:

Mucocutaneous bleeding
post-surgical haemorrhage
neonatal bleeding

Vitamin K is a fat-soluble vitamin, obtained from:

Dietary sources (especially green leafy vegetables)
Bacterial synthesis in the gut (colon flora)

Deficiency can present in two main contexts:

Newborns due to low placental transfer, immature liver, low vitamin K stores, and lack of gut flora (known as haemorrhagic disease of the newborn)
Later life due to malnutrition, fat malabsorption (biliary obstruction, pancreatic disease), prolonged antibiotics, or vitamin K antagonist therapy (warfarin)

Liver disease-associated coagulopathy

Pathophysiology:

Decreased synthesis of clotting factors (all except factor VIII)
Decreased fibrinogen in severe hepatocellular failure
Dysfibrinogenemia (abnormal fibrinogen function)
Increased Plasminogen activator → enhanced fibrinolysis
Decreased Thrombopoietin → thrombocytopenia
Hypersplenism (portal hypertension) → splenic sequestration of platelets
Biliary obstruction → vitamin K malabsorption
DIC may complicate severe disease
Net effect: Can be prothrombotic or haemorrhagic

Labs:

Prolonged PT
Prolonged aPTT
Low fibrinogen (in severe cases)
Thrombocytopenia

Disseminated intravascular coagulation (DIC)

Pathogenesis:

Widespread activation of coagulation → excess thrombin → fibrin deposition and platelet consumption
Simultaneous activation of fibrinolysis → fibrin degradation products (FDPs) interfere with fibrin polymerisation
Net result: consumptive coagulopathy (bleeding + thrombosis)

Causes:

Infection: Gram-negative sepsis, meningococcal sepsis, malaria
Malignancy: acute leukaemia, adenocarcinoma
Obstetric: amniotic fluid embolism, placental abruption, eclampsia
Hypersensitivity: anaphylaxis, incompatible transfusion
Tissue damage: trauma, burns, surgery
Vascular: leaking prosthetic valves, bypass surgery, aneurysms
Misc: liver failure, snake bites, pancreatitis, hypothermia, massive haemorrhage

Clinical features:

Bleeding: from venepuncture sites, wounds, GI tract, mucosa, urogenital tract, obstetric bleeding
Thrombosis: skin necrosis, renal failure, gangrene, cerebral ischaemia

Labs:

Decreased platelets
Decreased fibrinogen
Increased FDPs / D-dimer
Prolonged PT, aPTT, TT
Evidence of haemolysis

Management:
Treat underlying cause, supportive transfusion (FFP, platelets, cryoprecipitate); anticoagulation in select thrombotic cases

Autoantibody inhibition of coagulation

Specific inhibitors:

Acquired haemophilia A (autoantibodies to factor VIII) → severe bleeding

Non-specific inhibitors:

Lupus anticoagulant / antiphospholipid antibodies (often prothrombotic despite prolonged aPTT)

Miscellaneous causes

Diseases with M-protein production (e.g. multiple myeloma) → interference with coagulation
L-asparaginase therapy (decreased protein synthesis)
Anticoagulant therapies (Heparin, defibrinating agents e.g. snake venom, thrombolytic therapy)
Massive transfusion syndrome → dilutional coagulopathy (loss of clotting factors + platelets)
Uremia → platelet dysfunction (normal PT/aPTT, prolonged bleeding time)

Summary table

Cause	Pathophysiology	Labs	Clinical Features
Vitamin K deficiency (newborn, biliary obstruction, malabsorption, warfarin)	↓ vitamin K–dependent factors (II, VII, IX, X, protein C & S)	Prolonged PT (early), prolonged aPTT if severe, normal platelets	Mucocutaneous bleeding, surgical/postpartum haemorrhage, neonatal bleeding
Liver disease	↓ synthesis of clotting factors (except VIII), ↓ factor V & fibrinogen, dysfibrinogenemia, ↑ fibrinolysis, ↓ thrombopoietin, hypersplenism	Prolonged PT & aPTT, ↓ fibrinogen, thrombocytopenia	Bruising, mucosal bleeding, variceal haemorrhage, paradoxical thrombosis
DIC	Widespread thrombin activation → fibrin deposition, platelet & factor consumption, ↑ fibrinolysis → FDPs	↓ Platelets, ↓ fibrinogen, ↑ D-dimer, prolonged PT, aPTT, TT, evidence of haemolysis	Bleeding (venepuncture, mucosa, GI, obstetric) + thrombosis (skin necrosis, renal failure, CNS ischaemia)
Acquired hemophilia (specific inhibitor)	Autoantibodies against factor VIII	Isolated prolonged aPTT, normal PT, normal platelets	Severe spontaneous bleeding (soft tissue, mucosa, GI, GU)
Lupus anticoagulant (non-specific inhibitor)	Antiphospholipid antibodies interfere with phospholipid-dependent assays	Prolonged aPTT (not corrected on mixing), PT normal, platelets normal	Often prothrombotic (DVT, PE, miscarriage) despite prolonged aPTT
Miscellaneous (M-protein, L-asparaginase, heparin, thrombolytics, massive transfusion, uremia)	Protein interference, ↓ synthesis, drug effects, dilution, platelet dysfunction	Variable: heparin → prolonged aPTT, thrombolytics → low fibrinogen, massive transfusion → low platelets & factors, uremia → normal PT/aPTT but prolonged bleeding time	Bleeding tendency, sometimes thrombosis (esp. heparin-induced thrombocytopenia)

Coagulation pathway. Click on image to enlarge