Flashcards in Week 5 Deck (62):
von Willebrand Factor
Multimeric glycoprotein that is stored in platelets. binds to subendothelial collagen at sites of vascular injury, and binds to glycoprotein IB at the platelet surface. Also binds to and stabilizes coag. factor VIII
after plateets adhere to collagen, and increased intracellular Ca2+, phospholipase A2 is released which hydrolyzes membrane phospholipids liberating arachadonic acid
is a potent vasoconstrictor and inducer of platelet aggregation that functions by binding to receptors
Myosin Light Chain Kinase
Activated by released Ca2+ stores, phosphorylates the light chain of myosin which interacts with actin leading to platelet shape change.
Is a receptor for vonWildebrands factor and fibrinogen leading to fibrinogen induced platelet aggregation. It is inhibited by abciximab.
Protein which circulates in the blood, also found in platelet granules. Is composed of 3 pairs of polypeptide chains linked by disulfide bonds. Binds platelets helping them bind together.
Cleaves fibrinogen to fibrin which polymerize and form a soft clot with platelets. Also activates platelts by binding to specific receptors leading to phospholipase C leading to IP3 (Ca2+ release) and DAG (activates protein kinase C)
Initiated at the site of injury in response to tissue factor release which is a cofactor in the factor VIIa catalyzed activation of factor X
is an integral membrane protein that is expressed on surface of activated monocytes, and endothelial cells exposed to cytokines. Not found in plasma
Extrinsic pathway steps
Tissue injury leads to tissue factor which binds to and activates factor VII->VIIa. TF-VIIa can activate IX-> IXa. Factors IXa and Xa assemble with their non-enzymatic protein cofactors on the surface of aggregated platelets leading to large amounts of Xa and thrombin(IIa). and conversion of fibrinogen to fibrin... common pathway
also called the contact activation pathway, much less significant to hemostasis under normal physiological conditions than is the extrinsic. Hyperlipidemia or sepsis can lead to activation of thrombosis via the intrinsic clotting cascade.
Intrinsic pathway steps
Factor XII is converted to XIIa by HMWK collagen. Factor XIIa converts XI to XIa. XIa converts IX to IXa which binds VIIIa (which was activated by thrombin). IXa-VIIIa convert X->Xa. common pathway
IXa and VIIIa convert X to Xa in presence of Ca2+. Xa converts prothrombin(II) to thrombin using prothrombinase and factor Va(activated in minute amounts by increasing thrombin). Thrombin(IIa) converts fibrinogen to fibrin. Fibrin is cross linked by XIIIa (also activated by thrombin).
Most important thrombin inhibitor. inhibits activities of factors IXa, Xa, XIa and XIIa, plasmin, and kallikrein leading to clot dissolution. Activity is potentiated by heparin
Is on the surface of vessel endothelial cells, and regulates antithrombin III.
Is a trypsin like serine protease It uses Protein S as a cofactor. It, along with activated protein C degrade Va and VIIIa via proteolysis, decreasing thrombin production. Protein S anchors the activated Protein C complex to the clot. Activated protein C also stimulates endothelial cells to increase secretion of prostaglandin I2 which reduces platelet aggregation.
Involves the degradation of fibrin in a clot by plasminin.
is a serine protease that is formed by plasminogen. It degrades fibrin in a clot.
has a high affinity for fibrin, promoting the incorporation of plaminogen in the developing clot. it is mediated by activators which turn it to plasmin.
Tissue Plasminogen activator
Clears up clots especially in central lines.
is required in many factors for blood coagulation. It is needed for gamma carboxylation which occurs in the hepatocyte before clotting factor release.
is slow and long acting bloodanticoag. It competes with vitamin K and prevents gamma-carboxylation of glutamate residues in factors II, VII,IX,X, proteinsC and S. The factors cannot bind Ca2+or form the complexes necessary for the coagulation cascade to be initiated. IT DROPS PROTEIN C AND S LEVELS FIRST LEADING TO INCREASED CLOTTING AT FIRST. must bridge with heparin.
Binds to annd activates ATIII which leads to thrombin inactivation, blocks the activity of factors VIIIa, Ixa, Xa, and Xia by potentiating antithrombin 3 preventing a clot.
Released from T cells after binding with APC, supports growth and expansion of T, B and NK cell populations, can self activate
Made by Treg, Th2. Suppressor of T cell effector cells, blocks IL-2 and downregulation of T cell cytokines and MHC class II expression
(IFN y), made by M1 macrophages after Th1 cells stimulate them them with IFNy. Made by dendritic cells topromote the growth and survival of Th1, CD4+ cells and blocks the growth of Th2 cells
Also made by T-regs. blocks IL-1 and IL-2 dependant T cell proliferation.
produced by TH1 and activates M1 macrophages.
T cell doesn't get proper signaling including B7 from APC and dies off to control population.
it and IL-35 will turn a TH1 cell to a Treg cell.
B cell activation
CD4+ T cell must have CD40 ligand on it which will interact with CD40 on APC to activate them.
Thymus independent B cells B1
have CD5 on them, can be activated through TCR or BCR
Thymus independent B cells B2
BCR and costimulators, complement
allows T cells to hone in to migrate to the tymus .
master transcriptional regulator responds to input signal which then drives transcription of certain genes for Treg cells Tbet=Th1
an inborn lack of Treg cells is the cause of severe autoimmune inflammation in patients with this disease. Mutations in Foxp3.
TLR 4 deficiency
Involved in LPS detection, has deficiency found in africa, asia, and europe. results in higher increase in TNFa when stimulated with LPS, is better protection from cerebral forms of malaria.
immunodeficiency caused by a number of different genes, results with lack of T cell response.
contain fibrinogen, vWF
contain serotonin, ADP, Calcium
Tissue factor pathway inhibitor
The way that Xa shuts off the extinsic pathway on the tissue factor VIIa complex.
Protein C and S fx.
Shutdown factors VIII and V.
shuts down almost all parts of the pathway in both the intrinsic, extrinsic and common pathways.
Alternate to bleeding time, measures how quickly platelts occlude small holes in a membrane.
add aggegating agents to blood sample and see if platelts aggregate. Looking for platelet function abnormalities.
have known antigen bound to bottom of tray, and add patient serum which should contain antigen. Then add fluorescent antibody. The less light means the more antigen in the patient sample.
Have Antibody for antigen on bottom, add antigen/ sample, rinse, and then add same antibody but fluorescently labeled to dish and measure color
Lots of red cells stacked up together mostly only involved with myeloma.
Triad of Myeloma
Bone pain, renal failure, and anemia
von Willebrand Disease
most common bleeding disorder, autosomal dominant, variable severity. Mucosal bleedin in most patients, deep joint bleeding in severe cases. Prolonged bleeding time, PTT is prolonged, but normalizes with mixing study. INR: normal. Type I is absent vWF, Type II is deformed vWF.
X- linked recessive disorder. FACTOR VIII deficiency. Sx.- bleeding, deep, with possible joint deformities, and sometimes mucosal hemorrhage. INR, TT, Platelet count, bleeding time, all normal. PTT prolonged and corrected with Mixing study. Factor VIII low. DNA studies abnormal.
X- linked recessive, FACTOR IX deficiency. much less common than hemophilia A. same clinical findings and sx.
Disseminated Intravascular coagulation
Something leads to lots of clotting, using up all the clotting factors and platelets, then have bleeding problems. Have microangiopathic anemia. May be due to obstetric complications, adenocarcinoma, acute promyelocytic leukemia. Also could be from bacterial sepsis, trauma, burns, vasculitis, MOST (malignancy, Ob, Sepsis, and trauma).
Idiopathic Thrombocytopenic Purpura
diagnosis of exclusion. have autoantibodies to GP IIb-IIIa, or Ib, binds to platelets, machrophages eat platelts. Chronic: adult women, primary or secondary, see nosebleeds and easy bruising, can bleed on brain
Acute: kids, abrupt after viral ilness, self limiting, may be chronic
Thrombotic thrombocytopenic Purpura
pentad: MAHA(MicroAngiopathicHemolyticAnemia), thrombocytopenia, fever, neurologic defects, renal failure. It is a deficiency of ADAMTS13 which metabolizes vWF.
Is a traveling thrombus, often plugs up an artery.
Factor V Leiden
most common cause of unexplained thromboses. Point mutation in factor V gene, factor V cannot be turned off. Need genetic test for diagnosis. Mutated factor V gene. Cannot be cleaved by protein C. normal tests. Can only treat when a thrombus is present, with anticoagulant.
Antithrombin III deficiency
- it is a natural anticoagulant inhibiting just about everything, mutated gene produces less ATIII. Heparin doesn't work, antithrombin concentrates required.