BCP Week 2

Hemophilia

X-linked congenital deficiency of coagulation Factor VIII (type A- most common) or IX (type B). Intrinsic Pathway Recurrent hemarthroses and arthopathy Typically asymptomatic until trauma with unexpected excessive bleeding Tx: factor replacement

Formation of blood clot

a clot formation, formed by fibrin, occurs on top of the platelet plug (the final product)

Plasminogen

is activated to its active form, plasmin, by ____________ activators. In its active form it digests fibrin, therefore dissolving the clot

3 caused of Thrombocytopenia

occurs due to- 1) decreased bone marrow production 2) sequestration (usually in an enlarged spleen) 3) platelet destruction can be inherited or acquired risk of spontaneous bleeding (including petechial hemorrhage & bruising) occurs when platelets are < 10,000- 20,000/microliters

Prothrombin/ Thrombin Factor II

part of common pathway Converts fibrinogen to fibrin, also converts Factors V/VIII/XI to active forms produced in liver

Fibrin Stabilizing/ Factor XIIIa

part of common pathway helps fibrinogen stabilize to Fibrin I, probably released by platelets to strengthen Fibrin network produced by platelets

Fibrinogen/ Fibrin Factor I

part of common pathway lays down fibrous network for clot formation produced in Liver

Plasma Thromboplastin Antecedent/ Factor XIa

part of intrinsic pathway

Christmas Factor/ Factor IXa

part of intrinsic pathway converted to active form by factor XIa, teams up with factor VIIIa and IXa (intrinsic pathway) affected by warfarin lack of factor IX = Hemophilia B produced in Liver

Calcium Ions Factor IV

part of intrinsic, extrinsic, and common pathways necessary for all stages of coagulation always present, typically involved with converting factors to active forms produced in plasma

Primary Hemostasis

platelet aggregation and platelet plug formation. Platelets are activated in a multifaceted process, and as a result they adhere to the site of injury and to each other, plugging the injury.

Clot Retraction

platelets contract, via actin and myosin, causing compression and strengthening of the platelet plug

Pulmonary Embolism

thrombi detach from site of formation, embolize to vena cava -> R atrium -> R ventricle -> lodge in pulmonary arterial circulation (acute PE) unexplained breathlessness, pleurisy cough, hemoptysis major source of morbidity/mortality after DVT Tx: anti-coagulation (parentaral therapy bridged to warfarin or dabigatran

Common Pathway

Both instrinsic and extrinsic pathways eventually produce a prothrombin activator. The prothrombin activator triggers the "__________ ____________" in which prothrombin becomes thrombin followed by the conversion of fibrinogen to fibrin.

Conversion of prothrombin to thrombin

Conversion of ______________ to _______________ mediated by Factor Xa and Factor Va (together forming prothrombinase)

Conversion of fibrinogen to fibrin

Conversion of _______________ to ______________ mediated by Thrombin (IIa)

Disseminated Intravascular Coagulation

Etiology: caused by underlying pathology- sepsis, malignancy, obstetric cause, brain trauma. Purpura fulminans is severe form affecting skin, usu peds Patho: widespread fibrin formation in response

Vitamin K Deficiency

Etiology: most common in Neonates, adult post-broad spectrum antibiotics, GI absorption problem in small bowel, chronic liver disease, rarely due to low diet intake Patho: Deficiency inhibits coagulation factors (II, VII, IX, X), calcium binding, phospholipid membrane assembly, protein synthesis for bone, lung, kidney, placenta SSx: bleeding Workup: prolongation of PT value, low levels of clotting Factors II, VII, XI, X Tx: routine administration to all neonates, adults get parenteral Vit K

Obsolete Factor Factor VI

Factor VI

Formation of platelet plug

Formation of ______________ _________ called the initiation phase of coagulation. Platelets adhere to exposed collagen fibers of the injured vessel via von Willebrand factor (vWF), forming a bridge between the damaged vessel wall and platelets. This recruits more platelets. Then causes prothrombinase to begin cleaving prothrombin to thrombin.

Protein S

Functions as a cofactor to protein C in the inactivation of Factors VIIIa (intrinsic) and Va (common)

Fibrous Organization

Mediated by Thrombin. Formawtion of thrombin exerts positive feedback on its own production Factor XIII -> XIIIa via thrombin allows strengthening and stabilization of fibrin network

Vascular Constriction

Short-lived, inherent response to vessel damage, slows blood flow. Causes things to get sticky in damaged area.

Tissue Factor Pathway Inhibitor

binds to Factor VIIa (extrinsic) complexes and inhibits the ability of these complexes to generate Factor Xa (begins common). This anti-coagulation mechanism is the reason that the extrinsic pathway by itself can only generate small amounts of thrombin

Secondary Hemostasis

deposition of insoluble fibrin, which is generated by the proteolytic coagulation cascade. This insoluble fibrin forms a mesh that is incorporated into and around the platelet plug. This mesh serves to strengthen and stabilize the blood clot.

1st Physiologic Mechanism which prevents excessive thrombosis

first mechanism acts during the initiation phase of clotting and utilizes the plasma protein called tissue factor pathway inhibitor (TFPI), which is secreted mainly by endothelial cells. This substance binds to tissue factor-factor VIIa complexes and inhibits the ability of these complexes to generate factor Xa. This anticoagulant mechanism is the reason that the extrinsic pathway by itself can generate only small amounts of thrombin.

Antithrombin

inactivated the major clotting protein thrombin

Stuart-Prower/Factor Xa

intrinsic and extrinsic pathways (it starts the common pathway) activated by factor VII (from extrinsic pathway) or factors VIIIa and IXa (from intrinsic pathway), teams up with Va to convert Prothrombin to Thrombin affected by Warfarin Produced in Liver

2nd Physiologic Mechanism which prevents excessive thrombosis

mechanism is triggered by thrombin. Thrombin can bind to an endothelial cell receptor known as thrombomodulin. This binding eliminates all of thrombin's clot-producing effects and causes the bound thrombin to bind a particular plasma protein, protein C. The binding to thrombin activates protein C, which, in combo with another plasma protein, then inactivates factors VIIIa and Va. Thrombin directly activates factors VIII and V when the endothelium is damaged, and it also indirectly inactivates them via protein C in areas where the endothelium is intact.

Lysis of Blot Clots

mediated by plasmin formed by activation of plasminogen via plasminogen activators. Plasmin digests fibrin which then dissolving the clot. Fibrin degradation products are released, leading to inhibition of thrombin production. Byproducts include D-dimer.

Proaccelerin/ Factor Va

part of common pathway teams up with Xa to convert prothrombin to thrombin produced in liver

Tissue Thromboplastin/Tissue Factor Factor III

part of extrinsic factor released with tissue/vascular/traumatic injury activates extrinsic pathway (by activating factor VII) produced in tissue

Proconvertin/ Factor VIIa

part of extrinsic pathway activated by tissue factors, begins extrinsic factor, converts Factor X to active form (Xa) (extrinsic pathway) affected by Warfarin produced in liver

Hageman/ Factor XIIa

part of intrinsic pathway 1st step in intrinsic pathway activated by High Molecular Weight Kininogen when coagulation/clotting needs to happen converts XI to XIa produced in liver

Antihemophilic/ Factor VIIIa

part of intrinsic pathway activated by thrombin, assists factor IXa in converting Factor X to Xa (intrinsic pathway), lack of factor VIII = Hemophilia A produced in endothelial cells

3rd Physiologic Mechanism which prevents excessive thrombosis

third anticoagulant mechanism is a plasma protein called antithrombin III, which inactivates thrombin and several other clotting factors. The activity of antithrombin III is greatly enhanced when it binds to heparin, a substance present on the surface of endothelial cells. Antithrombin III prevents the spread of a clot by rapidly inactivating clotting factors that are carried away from the immediate site of the clot by the flowing blood.

Protein C

this protein is activated by binding of thrombin, this binding (in combination with Protein S) inactivated factors VIIIa (intrinsic) and Va (common)

Extrinsic Pathway

triggered by a chemical called tissue factor that is released by damaged cells. This pathway is "__________" because it's initiated by a factor outside the blood vessels. It's also known as the tissue factor pathway. (MEASURE BY aPPT)

Intrinsic Pathway

triggered by blood coming into contact with collagen fibers in the broken wall of a blood vessel. It's "____________" because it's initiated by a factor inside the blood vessel. It's sometimes called the contact activation pathway. (MEASURE BY PT)

Deep Vein Thrombosis

venous clots in lower extremity Normal arterial pulses and distal extremity perfusion Virchow's triad of hypercoagulability and endothelial injury → recruitment of activated platelets Thigh swelling, tenderness, erythema below level of thrombus. "Charley horse" persists and intensifies over days. + Homan's sign TX: clot dissolution via low-dose catheter directed thrombolysis