Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
48 Cards in this Set
- Front
- Back
|
4 factors that promote anticoagulation in small vessels
|
1. Heparin - Enhances ATIII (inactivates thrombin, IX, X, XI)
2. PGI2 (prostacyclin)- Vasodilator, inhibits platlet aggregation; synthesized from INTACT endothelial cells from PGH2 by prostacyclin synthase (this enzyme is NOT inhibited by ASA) 3. Protein C and S - Inactivate factors V and VIII, enhance fibrinolysis 4. tPA - activates plasminogen to release plasmin, which goes on to degrade coag factors and lyse fibrin clots (thrombi) |
|
|
5 factors that promote coagulation
|
1. TXA2 - Vasoconstrictor, enhances platelet aggregation; synthesized by platelets from PGH2 by thromboxane synthase, but PGH2 formation is INHIBITED IRREV by ASA and REVER by other NSAIDS (Inhibits COX)
2. vWF - Binds to exposed collagen and then platelets adhere to vWF promoting platelet adhesion, prevents degradation of VIII:C; synthesized by endothelial cells and megakaryocytes - platelets carry vWF in the alpha granules 3. Tissue thromboplastin (Factor III) - activates factor VII in the extrinsic pathway 4. Exposure of thromobogenic subendothelial collagen - activates XII 5. Decreased (intact) endothelial synthesis of antithromogenic substances - NO, PGI2, tPA |
|
|
What are the 2 platelet receptors
|
GpIb - binds vWF
GpIIb/IIIa - binds fibrinogen |
|
|
What Rx affect GpIIb/IIIa receptors
|
Ticlopidine and clopidogrel inhibit ADP-induced expression of the receptor
Abciximab - monoclonal Ab against GpIIb/IIIa receptor |
|
|
What is contained within the alpha granules of platelets
|
vWF and fibrinogen
|
|
|
What activates XII and what is the fxn of XIIa
|
1. Exposed subendothelial collagen
2. HMWK 1. Activates XI 2. Activates plasminogen - produces plasmin and activated plasminogen converts C3 to C3a 3. Activates kiniogen system - produces kallikrein from prekallikrein and bradykinin (incr vasodilation, permeability, pain) |
|
|
Fxn of factor XIII
|
Cross-links insoluble fibrin monomers
|
|
|
Fxn of vit K
|
Activated in liver by epoxide reductase (majority of vit k is syn by colonic bacteria) - activated vit K gamma-carboxylates the vit K dependent factors - Ca can then bind the carboxylated factors
|
|
|
MA of warfarin
Time period of anticoag |
Inhibits epoxide reductase and makes vit k nonfunctional
Anticoag doesn't immediately occur b/c still gamma carboxylated factors present - protein C and S decrease first, but prothrombin last - therefore heparin too (immediate anticoag by enhancing ATIII) |
|
|
What are the 2 main factors that activate plasminogen?
|
XII and tPA, which cause the release of plasmin
|
|
|
What factors are consumed in the formation of a clot
|
Fibrinogen (I), prothrombin (II), V, and VIII
|
|
|
What does plasmin produce
|
D-dimers = fragmented cross-linked fibrin monomers
|
|
|
Sequence of events that occurs in response to injury
|
Vascular, platelet, coagulation, and fibrinolytic
|
|
|
What characterizes the vascular phase
|
1. Transient vasoconstriction mediated by endothelin, exposure of tissue
2. Thromboplastin activates VII 3. Exposure of subendothelial collagen activates XII |
|
|
What characterizes the platelet phase of coag
|
vWF adheres to subendothelial collagen - platelets adhere to vWF by GpIb receptor - Platelets degranulate (release alpha granules and dense bodies i.e. ADP) - ADP promotes platelet agreggation (bind each by binding fibrinogen which binds IIb/IIIa) - platelets synthesize and release TXA2 - formation of temporary platelet plug
|
|
|
What does bleeding time test
|
Platelet function to formation of temporary plug
|
|
|
What does the Ristocetin cofactor assay test for
|
vWF
|
|
|
What are the 7 causes of prolonged bleeding time?
|
1. ASA or NSAIDS
2. Bernard-Soulier syndrome 3. Glanzmann's Dz 4. Renal failure 5. Scurvy 6. Thrombocytopenia 7. von Willebrand Dz |
|
|
Bernard-Soulier Dz
|
AR
Deficiency of GpIb receptor for vWF Defective platelet adhesion Thrombocytopenia and giant platelets |
|
|
Glanzmann's dz
|
AR
GpIIb/IIIa receptor deficiency for fibrinogen Defective platelet aggregation |
|
|
von Willebrand Dz
|
AD
Absent or defect vWF Platelet adhesion defect Decreased VIII survival ONLY one of the qualitiative platelet disorders that has an affect on coag as well - shows as an incr PTT MC hereditary coag disorder |
|
|
What does PT evaluate
|
VII (extrinsic down to formation of fibrin clot)
X, V, II, I Warfarin |
|
|
What does PTT evaluate
|
XII, IX, IX, VIII (intrinsic down to formation of fibrin clot)
X, V, II, I Heparin, NOT LMWH |
|
|
5 causes of thrombocytopenia
|
ITP (Acute and Chronic)
Heparin-induced HIV TTP HUS |
|
|
Acute ITP
|
MCC of thrombocytopenia in childern
Occurs after URI IgG Ab against IIb/IIIa receptors (Type II) Platelets are destroyed in the spleen by macrophages Respinds to CS |
|
|
Chronic ITP
|
MCC of thrombocytopenia in adults
SLE (1st manifestation), HIV IgG Ab against IIb/IIIa receptor (Type II) |
|
|
Heparin-induced thrombocytopenia
|
Marcophage removal of platelets - IgG Ab against heparin attached to PF4 (Type II)
|
|
|
HIV Thrombocytopenia
|
MC hematologic abn in HIV
|
|
|
TTP
|
Deficiency in vWF-cleaving metalloprotease - excess of vWF incr platelet adhesion to areas of endothelial cell injury
Platelets are consumed in formation of thrombi - causes thrombocytopenia Pentad: Thrombocytopenia Fever Renal failure Microangiopathic hemolytic anemia (schistocytes) Varying neuro Sx Lab:Decr platelet count - prolonged bleeding time Nml PT and PTT TX: plasmophoresis |
|
|
Lab values for ITP
|
Decr platelet count- prolonged bleeding time
Nml PT and PTT Increased megakaryocytes in bone marrow biopsy |
|
|
What does Fibrin degradation products (FDP) test
|
Fibrinolytic system
Increased in DIC NOT specific for DIC (like D-dimer) b/c FDP incr with lysis of fibrinogen AND fibrin thrombi (clots) D-dimer specific for fibrin thrombi |
|
|
Causes of primary thrombocytosis
|
ET, PCV
|
|
|
Causes of secondary thrombocytosis
|
Chronic iron deficiency
infection splenectomy malignancy |
|
|
Lab values in DIC
|
Decr Platelet count
Incr bleeding time Incr PT Incr PTT |
|
|
Difference in clinical finding b/w platelet and coagulation defects
|
Platelet - microhemorrhage: petechia, purpura, nose bleeds, Incr bleed time
Coag - Macrohemorrhage: Hemarthroses, easy bruising, Incr PT and/or PTT |
|
|
Hemophilia A
|
X-linked recessive
Factor VIII deficiency Hemarthroses, easy bruising Nml platelet / bleeding time Nml PT Incr PTT Tx: Factor VIII |
|
|
Hemophilia B
|
X-linked recessive
Factor IX deficiency Clinical identical to Hemophilia A |
|
|
Clinical findings of Von willebrands
|
Epistaxsis
Menorrhagia easy bruising Associated with angiodysplasia of the right colon |
|
|
Lab values of von Willebrands =
|
Incr bleeding time
Incr PTT Abd ristocetin test |
|
|
Tx of von Willebrands Dz
|
Desmopressin acetate (ADH analogue) - increases vWF and VIII
OCP - estrogen has similar action to desmopressin |
|
|
What is the 50:50 Mix test used for
|
Distinguish b/w circulating anticoagulants (Abs that destory coag factors) and decreased production of coag factors
No correction of PT and/or PTT = immune destruction Correction of PT and/or PTT = decreased production of anticoagulants |
|
|
Causes of vit K deficiency
|
1. Decreased syntheses
a. Newborn lack colonic bacteria, require IM vit K b. Abx 2. Malabsorption of fat soluble vit - celiacs 3. Cirrhosis - decr activation by epoxide reductase and decr synth of other factors |
|
|
Lab findings in liver Dz
|
Incr PT and PTT
Incr FDP and D-dimers Incr bleeding time |
|
|
Pathogenesis of DIC
|
Activation of coag system via tissue thromboplastin and exposed subendothelial collage
Thrombi develop and consume coag factors and platelets Fibrinolytic system is also activated by XII |
|
|
3 main factors involved in thrombus formation
|
Virchow's traid:
Endothelial injury Alteration in laminar flow Hypercoaguable state |
|
|
Acquired hypercoagulable states
|
1. Antiphospholipid syndrome - Associated with SLE and HIV, AP Ab contain anticardiolipin Ab and therefore get a false + to syphilis test
2. Malignancy 3. Folate or vit B12 deficiency - due to incr homocysteine 4.OCPs - estrogen increase syn of coag factors and decr ATIII 5. Pregnancy 6. Hyperviscosity - ET, PCV, Waldenstroms |
|
|
Inherited hypercoaguable states
|
Hx DVTs and PEs at early age
1. Factor V Leiden - MC, Mutant factor V cannot be degraded by protein C and S 2. ATIII deficiency - No prolongation of PT after injection of STD dose of heparin 3. Protein C and S deficiency - Cannot inactivate factors V and VIII |
|
|
What pts are at an increases likelihood of developing hemorrhagic skin necrosis when placed on warfarin
|
Protien C deficiency (inc heterozygote carriers (Asx)) - Protein C falls - incr V and VIII - causes cutaneous vessel thrombosis and skin necrosis
|
