PA H10 | Hemostasis & Bleeding Disorders — Glossary

An autoimmune disorder in which IgG autoantibodies develop spontaneously against factor VIII, causing a haemophilia-like bleeding disorder in adults without prior bleeding history or family history.

A clotting test that measures the intrinsic and common pathway; prolonged by factors VIII, IX, XI, XII deficiency, heparin, lupus anticoagulant, or common pathway defects.

AML subtype (FAB M3) with t(15;17) PML-RARA translocation; APL granules are rich in tissue factor, making this the haematological malignancy most strongly associated with DIC; ATRA treatment reverses DIC.

A metalloprotease enzyme that cleaves ultra-large von Willebrand factor multimers; its deficiency (inherited or antibody-mediated) causes TTP by allowing UL-vWF to spontaneously capture and activate platelets.

A serine protease inhibitor that neutralises thrombin, Xa, IXa, and other activated factors; its activity is potentiated 1,000-fold by heparin; deficiency causes thrombophilia.

Autosomal recessive qualitative platelet disorder caused by GPIb-IX-V deficiency; platelets cannot adhere to sub-endothelium; characterised by giant platelets and mild thrombocytopenia.

In-vivo or ex-vivo assessment of platelet-vessel interaction; prolonged when platelets are reduced or functionally impaired; normal in coagulation factor deficiencies alone.

The physiologically accurate model of coagulation in which clot generation occurs in three phases (initiation on tissue factor–bearing cells, amplification and propagation on platelet surfaces), replacing the classical intrinsic/extrinsic dichotomy.

The sequential enzymatic amplification pathway in which clotting factor zymogens are successively activated (intrinsic, extrinsic, and common pathways) to generate thrombin and ultimately a cross-linked fibrin clot.

The final shared sequence of coagulation — factor X activation → factor V → prothrombin (II) → thrombin → fibrinogen → fibrin — tested by both PT and aPTT. Defects here prolong both tests.

The depletion of platelets, fibrinogen, and coagulation factors (especially V and VIII) through their incorporation into diffuse microthrombi, resulting in a paradoxical haemorrhagic state.

The platelet enzyme responsible for thromboxane A2 synthesis; irreversibly inhibited by aspirin, impairing platelet activation for the entire platelet lifespan (7–10 days).

A fibrin degradation product containing cross-linked D fragments; its elevation confirms simultaneous clot formation and dissolution; used as a sensitive (not specific) screening test for DVT/PE.

A synthetic vasopressin analogue that releases vWF and factor VIII from endothelial Weibel-Palade bodies; effective in mild Haemophilia A and Type 1 vWD; contraindicated in Type 2B vWD.

Thrombocytopenia resulting from massive transfusion of packed red cells (which lack platelets) or cardiopulmonary bypass, diluting the circulating platelet mass.

A secondary pathological syndrome characterised by systemic activation of coagulation, leading to simultaneous microvascular thrombosis and haemorrhage due to consumption of platelets and clotting factors.

The tissue factor–initiated arm of the coagulation cascade involving tissue factor (factor III) and factor VII; the primary in vivo initiator; measured by the PT/INR.

A point mutation (Arg506Gln) in factor V that renders it resistant to inactivation by activated Protein C; the most common inherited thrombophilia, found in ~5% of Europeans.

Pro-coagulant cofactor synthesised by vascular endothelium (not hepatocytes); normal or elevated in liver disease, depleted by consumption in DIC — a key biochemical distinguisher between the two conditions.

Recombinant or plasma-derived concentrated preparation of factor VIII, used for prophylactic and on-demand treatment of Haemophilia A; also provides vWF in combination products for vWD.

Breakdown products of both fibrinogen and fibrin by plasmin; elevated in DIC and primary fibrinolysis; inhibit fibrin polymerisation and platelet aggregation.

A plasma-derived concentrate containing factors II, VII, IX, and X (all vitamin K-dependent) used for urgent reversal of warfarin anticoagulation or acute vitamin K-deficient haemorrhage.

A post-translational modification of glutamate residues in vitamin K–dependent coagulation factors, mediated by vitamin K–dependent carboxylase; essential for calcium-dependent binding to phospholipid surfaces.

Autosomal recessive qualitative platelet disorder caused by GPIIb/IIIa deficiency; platelets adhere normally but cannot aggregate, producing severe mucocutaneous bleeding with a normal platelet count.

Platelet surface glycoprotein that binds vWF during platelet adhesion; deficient in Bernard-Soulier syndrome.

Platelet surface receptor complex that binds von Willebrand factor exposed on damaged sub-endothelium, mediating platelet adhesion. Deficient in Bernard-Soulier syndrome.

Platelet surface integrin that, after activation, binds fibrinogen to bridge adjacent platelets during aggregation; the target of abciximab and eptifibatide; deficient in Glanzmann thrombasthenia.

The most abundant platelet surface receptor; binds fibrinogen to cross-link activated platelets during aggregation. Deficient in Glanzmann thrombasthenia; target of anti-platelet IgG in ITP.

Bleeding into a joint cavity; hallmark of severe coagulation factor deficiency, particularly haemophilia. Repeated episodes lead to haemophilic arthropathy.

X-linked recessive bleeding disorder caused by deficiency of factor VIII; characterised by deep-tissue bleeding, isolated prolonged aPTT, and normal PT and platelet count.

X-linked recessive bleeding disorder caused by deficiency of factor IX (Christmas factor); clinically identical to Haemophilia A but requires specific factor assays for diagnosis.

Progressive joint destruction resulting from repeated haemarthroses in severe haemophilia; pathologically characterised by iron-induced synovitis, cartilage degradation, and subchondral bone erosion.

Vitamin K deficiency bleeding in neonates caused by sterile gut (no K2 flora), poor placental vitamin K transfer, and low breast milk K1 content; prevented by routine intramuscular vitamin K at birth.

The physiological process that arrests bleeding after vascular injury while maintaining blood fluidity within intact vessels; comprises primary haemostasis, secondary haemostasis (coagulation), and fibrinolysis.

Systemic IgA-mediated leukocytoclastic vasculitis of small vessels presenting with a tetrad of palpable purpura, arthralgia, abdominal pain, and renal involvement, most common in children post-infection.

Autosomal dominant vascular disorder caused by mutations in endoglin or ALK1 (TGF-β pathway), leading to arteriovenous malformations in skin, mucosae, lungs, and brain; presents with recurrent epistaxis.

Sequestration of up to 90% of the platelet pool in an enlarged spleen (normally 30%), causing mild-to-moderate thrombocytopenia with normal or increased marrow megakaryocytes.

Autoimmune disorder characterised by IgG antibodies against platelet surface glycoproteins (GPIIb/IIIa), leading to splenic phagocytosis and isolated thrombocytopenia without an identifiable underlying cause.

An IgG alloantibody (in transfused haemophiliacs) or autoantibody (in acquired haemophilia) directed against a coagulation factor, neutralising its activity and preventing correction on the mixing study.

The contact-activation arm of the coagulation cascade involving factors XII, XI, IX, and VIII; measured by the aPTT; defects cause haemophilia A (VIII) or B (IX).

The International Society on Thrombosis and Haemostasis overt DIC score, assigning points to platelet count, PT prolongation, fibrinogen level, and D-dimer elevation; a score ≥ 5 indicates overt DIC.

Consumptive coagulopathy (chronic DIC) caused by a giant vascular tumour (haemangioma or kaposiform haemangioendothelioma) that traps and activates platelets and coagulation factors.

A phospholipid-dependent inhibitor that prolongs aPTT in vitro but causes thrombosis in vivo; it does not correct on the mixing study. Part of the antiphospholipid syndrome.

Large polyploid marrow cells that produce platelets by cytoplasmic fragmentation; their absence indicates production failure (aplasia), while their increase indicates peripheral destruction with compensatory upregulation.

Haemolytic anaemia caused by mechanical fragmentation of red cells as they pass through fibrin/platelet microthrombi in small blood vessels, producing schistocytes on peripheral film.

A diagnostic test in which patient plasma is mixed 1:1 with pooled normal plasma; correction of a prolonged clotting time indicates a factor deficiency, while non-correction indicates an inhibitor.

Pinpoint (1–3 mm) non-blanching haemorrhagic spots in skin or mucosae caused by red cell extravasation from capillaries, characteristic of thrombocytopenia or platelet dysfunction.

Proteins Induced by Vitamin K Absence or Antagonism; structurally complete but functionally inert coagulation factors lacking Gla residues, produced when vitamin K is depleted or warfarin is administered.

The active serine protease of fibrinolysis, generated from plasminogen by tPA or uPA; degrades fibrin into FDPs and D-dimer.

The initial response to vascular injury consisting of vasoconstriction and formation of the loose platelet plug via platelet adhesion, activation, and aggregation.

Regular infusion of factor concentrate started before the first joint bleed in severe haemophilia (typically age 1–2 years), aimed at preventing haemophilic arthropathy by maintaining factor levels above the spontaneous-bleed threshold.

A vitamin K–dependent anticoagulant zymogen activated by thrombin-thrombomodulin complex; activated Protein C (with Protein S) degrades Va and VIIIa; deficiency causes venous thrombophilia; warfarin depletes it early due to its short half-life (~8 hours).

A vitamin K–dependent cofactor for activated Protein C that enhances degradation of Va and VIIIa; both Protein S and Protein C are reduced by warfarin; deficiency causes thrombophilia.

A clotting test that measures the time to clot formation via the extrinsic and common pathway; prolonged by factor VII deficiency, warfarin, liver disease, or common pathway factor deficiency.

A coagulation test that measures the function of the extrinsic and common pathways (factors VII, X, V, II, and fibrinogen); reported as seconds or as INR.

Confluent, non-blanching haemorrhagic lesions > 3 mm caused by bleeding into the skin; may be flat (thrombocytopenic) or palpable (vasculitic).

A severe, life-threatening complication of DIC characterised by haemorrhagic necrosis of skin from extensive dermal vessel thrombosis; often seen in meningococcal sepsis.

A functional test for vWF in which ristocetin (an antibiotic) is added to platelet-rich plasma; normal vWF causes platelet agglutination. Reduced agglutination indicates vWF deficiency or dysfunction.

Fragmented red cell forms (helmet cells, triangle cells) seen on peripheral blood film in microangiopathic states such as TTP, HUS, and DIC; their presence implies intravascular red cell fragmentation.

Vitamin C deficiency causing impaired hydroxylation of collagen's proline and lysine residues, leading to structurally weak vessel walls and perifollicular haemorrhages, gingival bleeding, and subperiosteal haemorrhages.

Activation of the fibrinolytic system (plasmin generation) in response to widespread fibrin deposition in DIC; produces FDPs and D-dimer that further impair haemostasis.

Age-related purpura from atrophy of perivascular connective tissue, producing easy bruising on sun-exposed skin (dorsum of hands, forearms); platelet count and coagulation tests are normal.

The enzyme complex of factors IXa and VIIIa assembled on a phospholipid surface that activates factor X in the intrinsic pathway; disrupted in Haemophilia A (no factor VIII) and Haemophilia B (no factor IXa).

The central effector serine protease of haemostasis; cleaves fibrinogen to fibrin, activates factors V, VIII, XIII, and platelets, and on intact endothelium activates Protein C as an anticoagulant feedback mechanism.

Platelet count < 150,000/µL; spontaneous mucocutaneous bleeding typically occurs below 20,000/µL.

An endothelial surface protein that binds thrombin and redirects it from a pro-coagulant to an anticoagulant role by activating Protein C; integral to the physiological anti-thrombotic function of intact endothelium.

A prostaglandin synthesised by activated platelets via cyclooxygenase from arachidonic acid; promotes platelet activation, aggregation, and vasoconstriction; irreversibly blocked by aspirin.

A transmembrane glycoprotein expressed by sub-endothelial cells and activated monocytes that initiates the extrinsic coagulation pathway by forming a complex with factor VII; the primary trigger of DIC in sepsis and obstetric emergencies.

An endothelial-derived inhibitor that inactivates the TF–VIIa–Xa complex, limiting extrinsic pathway activation to the initiation phase; explains why intrinsic amplification is required for sustained coagulation.

An endothelial-derived serine protease that converts plasminogen to plasmin on fibrin surfaces; the basis of thrombolytic therapy (alteplase) in acute MI and stroke.

Recurrent migratory thrombophlebitis in visceral malignancy (classically pancreatic or gastric carcinoma) representing chronic compensated DIC driven by tumour-derived tissue factor and mucin.

Life-threatening thrombotic microangiopathy caused by ADAMTS13 deficiency, characterised by a pentad: MAHA (schistocytes), thrombocytopenia, neurological abnormalities, renal dysfunction, and fever.

The enzyme that recycles vitamin K epoxide back to active reduced vitamin K (KH₂); the target of warfarin and other coumarin anticoagulants.

Clotting factors (II, VII, IX, X) and anticoagulant proteins (Protein C, Protein S) that require vitamin K for γ-carboxylation of glutamate residues, enabling calcium binding and membrane assembly; all are reduced by warfarin.

The commonest inherited bleeding disorder, caused by quantitative or qualitative deficiency of vWF; presents with mucocutaneous bleeding and variable aPTT prolongation. Autosomal inheritance.

A large multimeric glycoprotein synthesised by endothelial cells that mediates platelet adhesion under high shear stress by bridging subendothelial collagen to platelet GPIb receptor; also acts as a carrier protein for factor VIII.

Secretory granules found in vascular endothelial cells that store vWF multimers (and factor VIII) and release them in response to stimuli including DDAVP, thrombin, and histamine.

Modified glutamate residues on vitamin K-dependent factors created by γ-carboxylation; chelate calcium ions and enable factor binding to phospholipid surfaces necessary for tenase and prothrombinase complex formation.

Post-translational modification of specific glutamate residues on vitamin K-dependent coagulation factors (II, VII, IX, X) by γ-glutamyl carboxylase; requires vitamin K and creates γ-carboxyglutamate (Gla) residues essential for calcium and phospholipid binding.