Chapter 6 - Abnormalities of Blood Coagulation

What causes abnormality of small blood vessels?

Small blood vessels fail to constrict after injury or have formed abnormalities - leads to abnormal bleeding (relatively rare)

How is prothrombin converted into thrombin?

- by prothrombin activator and plasma factors

What happens in the conversion of fibrinogen to fibrin

- thrombin splits fibrinogen into smaller molecules = fibrin - fibrin strands join end to end to form a net

What is treatment for DIS?

- treated with heparin initially - if severe, platelet/plasma transfusions

What causes deficiency of one or more plasma coagulation factors?

- Hemophilia: x linked, hereditary -- repeated episodes of hemmorghage in joins and internal organs after minor injury - hemophilia A: missing factor VIII - hemophilia B: missing factor IX (aka Christmas factor) - ^^ treat with artificial injections - Von willebrand disease: missing VWF - framework for platelet to attach to damaged vessel wall (prevents clot formation)

What happens in prothrombin activator generation phase?

- Intrinsic system derives components from blood - Extrinsic system derives components from tissue - both interact to initiate clotting - generate thromboplastin to form prothrombin activator

What are signs/symptoms of DIS?

- bleeding from mouth, nose, incisions - no clotting - no platelets or clotting factors

What are some causes of disturbances of Phase 2 of the coagulation cascade?

- deficiency of prothrombin or factors required to convert prothrombin into thrombin CAUSES: - administration of anticoagulant drugs - can't synthesize clotting factors - inadequate vitamin K synthesis - result of prolonged antibiotic use - inadequate vitamin K absorption - if common bile duct blocked by gallstones or tumor bile can't enter intestine (need bile to absorb) - severe liver disease - can't synthesize coagulation factors SIGNS/SYMPTOMS: large hematoma (internal hemorrhage)

What roles do antithrombin have in regulating blood coagulation?

- inhibits thrombin and other coagulation factors

What are some causes of thrombocytopenia?

- injury or disease of bone marrow - infiltration of bone marrow by leukemic or cancer cells - anti-platelet antibodies destroy peripheral circulating blood platelets (autoimmune)

What are petechiae and what causes them?

- pinpoint hemorrhages of small capillaries - in skin or mucous membranes - present as small red or blue spots (1-5 mm) - indicate defective or inadequate platelets - OR a capillary defect

What are the 4 classes of disturbances in blood coagulation?

1. Abnormality of small blood vessels 2. Abnormality of platelet formation 3. Deficiency of one or more plasma coagulation factors (proteins) 4. Liberation of thromboplastic material into circulation (presence in bloodstream)

What are some causes of thromboplastin being released into circulation?

1. Diseases associated with shock and tissue necrosis 2. Overwhelming bacterial infections 3. Other causes of tissue necrosis - release of thromboplastic material into bloodstream = widespread intravascular coagulation = DIS

What are the factors concerned with hemostasis?

1. Integrity of small blood vessels (first line of defense, if not functioning other steps suffer) 2. Adequate numbers of platelets (to form plugs) 3. Normal amounts of coagulation factors 4. Normal amounts of coagulation inhibitors 5. Adequate amounts of calcium ions in the blood (usually not an issue because it will cause bigger problems first)

What 3 functions do platelets play in hemostasis?

1. PLUG defect in vessel wall (temporary) 2. Liberate vasoconstrictors - serotonin, heparin (cause platelets to AGGREGATE) 3. Release substances that INITIATE coagulation

What are the 3 phases of blood coagulation

1. Prothrombin activator is generated (from thromboplastin) 2. Conversion of prothrombin into thrombin 3. Conversion of fibrinogen into fibrin (by thrombin)

Explain the steps in blood clotting (broadly)

1. Vascular spasm - smooth muscle contracts 2. Platelet plug formation (platelets release chemicals that make nearby platelets sticky = plug) 3. Coagulation = fibrin mesh

What is hemostasis?

Arrest of bleeding caused by activation of blood coagulation mechanism (blood-equilibrium)

What roles do small vessels play in hemostasis?

First line of defense against excessive bleeding - constrict when injured - limit blood loss - make opening smaller - expose connective tissue, causing platelet adhesion and activate coagulation - work with platelets to initially stop blood loss

What are some causes of disturbances of Phase 1 of the coagulation cascade?

Hemophilia: hemorrhage in joints and internal organs after minor injury Von willebrand disease: autosomal dominant - prevents clot formation

What roles do plasmin have in regulating blood coagulation?

Plasmin dissolves fibrin after its formed - plasmin = fibrinolysin - plasminogen is trapped in clot and activated to form plasmin - fibrinolytic process initiated at same time as coagulation cascade but is a slower process: days-weeks as tissue heals

What is thrombocytopenia?

Platelet deficiency

What are coagulation factors and inhibitors?

Proteins produced by the liver, which circulate inactively

What roles do coagulation inhibitors play in regulating blood coagulation?

Restrict clotting to limited area - only where necessary

What causes abnormality of platelet formation?

Thrombocytopenia (low platelets) - injury or disease of bone marrow, damages megakaryocytes (platelet precursors) - leukemic or cancer cells infiltrate bone marrow - crowd out megakaryocutes - antiplatelet antibodies destroy peripheral blood platelets (autoimmune disease) - OR platelets function abnormally despite normal count

What is disseminated intravascular coagulation syndrome?

When thromboplastic substances are released into the blood stream - this causes activation of coagulation mechanism - whole body clots - fibrinolytic mechanism activated - whole body bleeds - no factors left for clots