Pathoma Chapter 4: Hemostasis and Related Disorders

High-yield vocabulary flashcards covering the pathophysiology of primary and secondary hemostasis, bleeding disorders, thrombosis, and embolism based on Pathoma Chapter 4.

Hemostasis

The process of stopping bleeding and keeping blood within damaged vessels by forming a localized thrombus at the site of vascular injury.

Primary Hemostasis

The initial stage of hemostasis that forms a weak platelet plug via interactions between platelets and the disrupted blood vessel wall.

Secondary Hemostasis

The second stage of hemostasis that stabilizes the initial weak platelet plug through the coagulation cascade, ultimately generating fibrin.

Transient Vasoconstriction

The immediate, initial step of primary hemostasis mediated by reflex neural stimulation and endothelin release from endothelial cells to reduce blood loss.

Endothelin

A potent vasoconstrictive peptide released from damaged endothelial cells that mediates immediate transient vasoconstriction.

von Willebrand Factor (vWF)

A bridging molecule derived from endothelial Weibel-Palade bodies and platelet $\alpha$-granules that binds exposed subendothelial collagen to platelet GPIb receptors during adhesion.

Weibel-Palade Bodies

Storage granules within endothelial cells that contain von Willebrand factor (vWF).

Platelet Adhesion

The process whereby platelets bind to exposed subendothelial collagen via the interaction of the platelet surface receptor GPIb with von Willebrand factor (vWF).

Glycoprotein Ib (GPIb)

The platelet surface receptor that binds to von Willebrand factor (vWF) during platelet adhesion.

Adenosine Diphosphate (ADP)

A mediator released from platelet dense granules upon activation that promotes surface exposure of the GPIIb/IIIa receptor.

Thromboxane $A_2$ ($TXA_2$)

A mediator synthesized by platelet cyclooxygenase (COX) and released during degranulation that promotes platelet aggregation.

Glycoprotein IIb/IIIa (GPIIb/IIIa)

A platelet surface receptor that binds plasma fibrinogen, allowing platelets to link to one another during platelet aggregation.

Platelet Aggregation

The clumping of platelets together at the site of injury via GPIIb/IIIa receptors using circulating fibrinogen as a bridging molecule.

Quantitative Platelet Disorder

A primary hemostasis disorder characterized by a decreased number of platelets (thrombocytopenia).

Qualitative Platelet Disorder

A primary hemostasis defect characterized by abnormal platelet function despite an adequate platelet count.

Epistaxis

Nosebleeding; noted as the most common overall symptom of mucosal bleeding seen in primary hemostasis disorders.

Petechiae

Pinpoint skin hemorrhages measuring $1\text{--}2\,mm$ that signify thrombocytopenia and are not usually seen in qualitative platelet disorders.

Purpura

Skin hemorrhages measuring $> 3\,mm$ in size, intermediate between petechiae and ecchymoses.

Ecchymoses

Large cutaneous hemorrhages or bruises measuring $> 1\,cm$ in size.

Normal Platelet Count

A standard laboratory reference range of $150\text{--}400 \times 10^3\,\mu L^{-1}$ ($150\text{--}400\,K/\mu L$); symptoms typically manifest when counts drop to $< 50\,K/\mu L$.

Bleeding Time

A clinical laboratory test of platelet function and primary hemostasis with a normal reference range of $2\text{--}7\,minutes$; prolonged in both quantitative and qualitative platelet disorders.

Megakaryocyte

A large bone marrow precursor cell responsible for producing platelets; assessed via bone marrow biopsy to differentiate platelet underproduction from peripheral destruction.

Immune Thrombocytopenic Purpura (ITP)

The most common cause of thrombocytopenia in children and adults, driven by autoimmune IgG production against platelet antigens such as GPIIb/IIIa.

Acute ITP

A self-limited form of ITP that typically arises in children weeks after a viral infection or immunization, resolving spontaneously within weeks.

Chronic ITP

A persistent form of ITP typically seen in adults, classically women of childbearing age, which may be primary or secondary to conditions such as SLE.

Intravenous Immunoglobulin (IVIG)

A medical therapy used in ITP to rapidly and temporarily raise the platelet count during symptomatic bleeding by saturating splenic macrophage Fc receptors.

Splenectomy in ITP

A surgical intervention for refractory ITP that removes both the primary site of anti-platelet antibody synthesis (plasma cells) and the site of platelet destruction (macrophages).

Microangiopathic Hemolytic Anemia (MAHA)

A form of hemolytic anemia caused by mechanical shearing of RBCs as they navigate through pathologic platelet microthrombi in small blood vessels, generating schistocytes.

Schistocytes

Mechanically fragmented, sheared red blood cells visible on a peripheral blood smear in microangiopathic hemolytic anemias (e.g., TTP, HUS, and DIC).

Thrombotic Thrombocytopenic Purpura (TTP)

A microangiopathic disorder characterized by platelet microthrombi and thrombocytopenia caused by an acquired autoantibody against the cleaving enzyme ADAMTS13, seen predominantly in adult females.

ADAMTS13

An enzyme that normally cleaves large, highly thrombogenic vWF multimers into smaller monomers; deficiency leads to uncleaved multimers that trigger abnormal platelet microthrombi.

Hemolytic Uremic Syndrome (HUS)

A microangiopathic condition classically seen in children following gastrointestinal infection by E. coli O157:H7 from undercooked beef, predominantly involving renal microthrombi.

Verotoxin (Shiga-like Toxin)

An enterotoxin produced by E. coli O157:H7 that directly damages endothelial cells in the kidneys and microvasculature, leading to platelet aggregation and microthrombi formation.

Bernard-Soulier Syndrome

A qualitative platelet disorder caused by an inherited deficiency of GPIb, resulting in impaired platelet adhesion and a blood smear showing enlarged platelets with mild thrombocytopenia.

Glanzmann Thrombasthenia

A qualitative platelet disorder caused by an inherited genetic deficiency of the GPIIb/IIIa receptor, leading to severely impaired platelet aggregation.

Aspirin (Mechanism in Platelets)

An antiplatelet agent that irreversibly inactivates cyclooxygenase (COX), blocking $TXA_2$ synthesis and thereby impairing platelet aggregation.

Uremic Thrombopathy

A qualitative defect in which the buildup of nitrogenous waste products in kidney failure disrupts platelet function, impairing both adhesion and aggregation.

Thrombin

A key serine protease generated by the coagulation cascade that cleaves soluble plasma fibrinogen into insoluble fibrin monomers to stabilize the platelet plug.

Tissue Factor (Tissue Thromboplastin)

A subendothelial activator released upon tissue injury that binds and activates Factor VII, triggering the extrinsic pathway of the coagulation cascade.

Factor XII

The contact-activated clotting factor that initiates the intrinsic pathway of the coagulation cascade upon exposure to subendothelial collagen.

Hemarthrosis

Bleeding into joint spaces, a hallmark clinical feature of secondary hemostasis disorders (coagulation factor deficiencies).

Prothrombin Time (PT)

A coagulation test that measures the integrity of the extrinsic (Factor VII) and common (Factors II, V, X, and fibrinogen) pathways.

Partial Thromboplastin Time (PTT)

A coagulation test that measures the integrity of the intrinsic (Factors XII, XI, IX, VIII) and common (Factors II, V, X, and fibrinogen) pathways.

Hemophilia A

An X-linked recessive bleeding disorder caused by a genetic deficiency of Factor VIII, presenting with deep tissue, joint, and postsurgical bleeding, elevated PTT, and normal PT.

Hemophilia B (Christmas Disease)

An X-linked recessive bleeding disorder caused by a genetic deficiency of Factor IX, clinically and biochemically identical to Hemophilia A except for decreased Factor IX levels.

Coagulation Factor Inhibitor

An acquired autoantibody directed against a specific clotting factor (most commonly anti-Factor VIII), causing clinical bleeding and prolonged PTT that does not correct with normal plasma mixing.

Mixing Study

A diagnostic laboratory assay combining patient plasma with normal pooled plasma; a prolonged PTT corrects if there is a factor deficiency, but fails to correct if an inhibitor is present.

von Willebrand Disease (vWD)

The most common inherited coagulation disorder, typically autosomal dominant, causing defective platelet adhesion, increased bleeding time, and reduced Factor VIII stability with elevated PTT.

Ristocetin Test

An in vitro diagnostic assay where ristocetin induces platelet agglutination in the presence of functional vWF and GPIb; agglutination is characteristically abnormal/impaired in von Willebrand disease.

Desmopressin (DDAVP)

A synthetic vasopressin ($ADH$) analog used to treat von Willebrand disease by stimulating endothelial Weibel-Palade bodies to release stored vWF.

Vitamin K Epoxide Reductase

A hepatic enzyme that converts inactive oxidized vitamin K to its active reduced state, an enzymatic step inhibited by warfarin.

Gamma ($\gamma$)-Carboxylation

A post-translational enzymatic modification catalyzed by activated vitamin K that adds carboxyl groups to Factors II, VII, IX, X, and proteins C and S, enabling them to bind calcium.

Dilutional Coagulopathy

A relative deficiency of coagulation factors resulting from massive volume fluid resuscitation or large-volume packed RBC transfusions without adequate plasma replacement.

Heparin-Induced Thrombocytopenia (HIT)

A complication of heparin therapy wherein platelet destruction leads to thrombocytopenia while destroyed platelet fragments paradoxically activate surviving platelets, causing thrombosis.

Disseminated Intravascular Coagulation (DIC)

A life-threatening syndrome involving widespread, pathologic activation of the coagulation cascade, causing systemic microthrombi and ischemia along with massive consumption of platelets and clotting factors leading to bleeding.

D-dimer

A specific fibrin degradation product derived exclusively from plasmin-mediated breakdown of cross-linked fibrin; elevated levels serve as the best screening test for DIC.

Tissue Plasminogen Activator (tPA)

An endothelial-derived enzyme that converts inactive plasminogen to active plasmin to initiate physiological fibrinolysis.

Plasmin

An active fibrinolytic enzyme that degrades cross-linked fibrin, cleaves serum fibrinogen, destroys clotting factors, and inhibits platelet aggregation.

Alpha-2-Antiplasmin ($\alpha_2$-antiplasmin)

A circulating regulatory protein that binds and rapidly inactivates free plasmin to prevent excessive systemic fibrinolysis.

Disorder of Fibrinolysis

A bleeding state caused by plasmin overactivity (e.g., following radical prostatectomy or in liver cirrhosis) that presents with elevated PT/PTT, prolonged bleeding time, and increased fibrinogen split products without D-dimers.

Aminocaproic Acid

An antifibrinolytic therapeutic agent that treats disorders of fibrinolysis by competitively inhibiting plasminogen activation.

Thrombus

A pathologic intravascular blood clot formed during life, attached to the vessel wall, and characterized histologically by alternating layers known as lines of Zahn.

Lines of Zahn

Microscopic alternating laminations of pale platelets/fibrin and dark red blood cells that demonstrate a thrombus formed in flowing blood, distinguishing it from a postmortem clot.

Virchow Triad

The three primary pathophysiologic determinants that predispose to intravascular thrombosis: endothelial injury, alterations in normal blood flow (stasis or turbulence), and hypercoagulability.

Prostacyclin ($PGI_2$)

An endothelial eicosanoid product that promotes vasodilation and strongly inhibits platelet activation and aggregation.

Nitric Oxide (NO)

An endothelial-derived gas that mediates smooth muscle relaxation (vasodilation) and suppresses platelet adhesion and aggregation.

Antithrombin III (ATIII)

A physiological circulating anticoagulant augmented by endothelial heparin-like molecules that directly binds and inactivates thrombin and other activated clotting factors.

Thrombomodulin

An endothelial surface receptor that binds thrombin and redirects its enzymatic activity to activate Protein C, shifting thrombin from a procoagulant to an anticoagulant enzyme.

Protein C and Protein S

Vitamin K-dependent natural anticoagulant proteins that complex together to inactivate activated cofactors Factor V and Factor VIII.

Warfarin Skin Necrosis

Microvascular cutaneous thrombosis caused by rapid depletion of short half-life Protein C and S relative to procoagulant factors II, IX, and X at the onset of warfarin therapy, particularly in patients with preexisting Protein C or S deficiency.

Factor V Leiden

The most common inherited hypercoagulable state, characterized by a point mutation in Factor V that eliminates its cleavage site, rendering it resistant to inactivation by activated Protein C.

Prothrombin 20210A

An inherited point mutation in the 3' untranslated region of the prothrombin gene that elevates prothrombin mRNA expression, increasing plasma prothrombin levels and thrombosis risk.

Cystathionine Beta Synthase (CBS) Deficiency

An inborn error of metabolism characterized by elevated homocysteine levels, homocystinuria, vessel thrombosis, intellectual disability, lens dislocation, and long slender fingers (arachnodactyly).

Embolus

An intravascular solid, liquid, or gaseous mass that is carried by blood flow from its site of origin to a distant site, where it can lodge and cause tissue occlusion.

Thromboembolus

A dislodged, travelling fragment of an intravascular blood clot, accounting for $> 95\%$ of all clinical embolisms.

Atherosclerotic Embolus

An embolus resulting from the dislodgement of an atheromatous plaque, identified histopathologically by cholesterol clefts within the occluded vessel lumen.

Fat Embolus

An embolus associated with fractures of long bones (e.g., femur) or soft tissue trauma, classically presenting with dyspnea, neurologic symptoms, and a petechial rash over the chest.

Gas Embolus (Decompression Sickness)

An embolism caused by nitrogen gas precipitating as bubbles within blood and tissues following rapid ascent by a deep-sea diver, presenting with the 'bends' (joint/muscle pain) and the 'chokes' (respiratory distress).

Caisson Disease

A chronic form of decompression sickness characterized by multifocal ischemic necrosis of bone resulting from gas bubble occlusion in the skeletal microvasculature.

Amniotic Fluid Embolism

An obstetric emergency wherein amniotic fluid enters maternal circulation during labor or delivery, manifesting as acute dyspnea, neurologic compromise, and DIC, with squamous cells and keratin debris found in pulmonary microvessels.

Pulmonary Embolism (PE)

Occlusion of the pulmonary arterial bed, most commonly caused by thromboemboli originating from the deep veins of the lower extremities (DVT).

Saddle Embolus

A large thromboembolus straddling the bifurcation of the main pulmonary artery into the right and left pulmonary arteries, capable of causing instantaneous death via electromechanical dissociation.

Pulmonary Infarction

Necrosis of lung parenchyma seen in approximately $10\%$ of pulmonary embolisms, typically grossing as a hemorrhagic, wedge-shaped infarct with its base abutting the pleura.

Systemic Embolism

An arterial embolus that originates within the arterial tree—most commonly arising from the left side of the heart—and travels down systemic circulation to occlude organs, particularly the lower extremities.