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61 Cards in this Set
- Front
- Back
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Sex linked recessive diseases: Hemophilia A and Hemophilia B are due to a deficiency in which factors:
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Factor VIII
Factor IX |
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A deficiency of this coagulation factors is not associated with bleeding:
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Factor XII
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The final blood clot is stabilized by the formation of covalent bonds between adjacent fibrin monomers is due to the action of this clotting factor:
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XIII
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Define term:
Prothrombin time |
A laboratory tests that combines patient plasma, calcium and thromboplastin --> fibrin clot: require normal levels of: VII, X, V, II and fibrinogen
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Define term:
Activated plasma prothrombin time: |
A laboratory tests that combines patient plasma,phospholipid, calcium and an activator -->fibrin clot: require normal levels of: XII, XI, IX, VIII, V,II and fibrinogen
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Define term:
Thrombin time |
A follow up test after PT and APTT. It is performed by addition of thrombin directly to citrated plasma without adding Ca++. It is prolonged if there is a deficiency of fibrinogen or in the presence of thrombin inhibitors eg. heparin
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MOA of coumarin:
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Inteferes with vitamin K dependent post-translational B-carboxylation. Affects factors II, VII, IX and X
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Role of vitamin K as an anticoagulant:
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Vitamin K is a cofactor in carboxylation system --> This system adds an extra carboxyl gp to (10 - 12) carboxyl gps near N terminus of the Glutamase AA in coagulation factors that are vitamin K dependent --> These factors can now strongly bind Ca++ --> And through this, they can bind to anion in phospholopid surfaces.
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What is the MOA of Heparin?
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It is highly sulfated --> Binds to Antithrombin ( a plasma protein) --> Antithrombin is now 1000x more able to bind and neutralize activity of THROMBIN and FACTOR Xa.
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Why are patients on anticoagulants first given heparin and coumadin, and 3-5 days later stop taking heparin and continue with coumadin?
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The anticoagulation effects of coumadin do not occur until 3-5 days later due to the half lives of vitamin K-dependent half lives.
4-6hrs: Factor VII 1-2 days: Factors IX and X 3 days: Prothrombin |
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These two substances are secreted by endothelial cells, and are inhibitors of platelet aggregation:
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NO and Prostacyclin (PGI2)
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Name two vitamin K dependent zymogens that are part of the negative feedback mechanism that is set up once coagulation has began with the elaboration of thrombin:
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Protein C and protein S
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After a clot has already been formed within a blood vessel, the fibrinolytic 'task force' is called in to play and the key enzyme is:
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Plasmin, has a high affinity for fibrin and tends to be localized within the clot itself.
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What are the essential elements in clinical hx when evaluating a patient for possible bleeding disorder?
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Was bleeding spontaneous or after injury
How severe was bleeding episode? --> How long did it take to recover?--> What Rx was needed to stop bleeding? Have you required blood transfusion of given iron for anemia? Was bleeding immediate or delayed? Family hx? Any medications? Type of bleeding? When was the first episode? |
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What does the von Willebrand evaluation measure?
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Amount of von Willebrand protein
Amount of Factor VIII that the factor is carrying Functional acitivity in the presence of ristocetin |
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How do you distinguish the difference between severe, moderate and mild disease in patients with hemophilia A and B?
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Char of mild disease:
+ Trauma induced bleeding only Char of moderate disease: +In btw mild and severe Char of severe disease: + Spontaneous joint and muscle hemorrhage +Easy bruising +Prolonged and potentially fatal post op hemorrhage +Normal response to abrasions and superficial cuts. |
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What are the presenting signs and symptoms of a patient with hemophilia A and B?
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+ Normal PT
+ Prolonged PTT + Normal platelet count + Young male (mostly) + X-linked inheritance |
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How is hemophilia treated?
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Factor replacement, main complication with this is the development of antibodies to the factors being administered to the patient.
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vW is primarily synthesized by:
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Endothelial cells and megakaryocytes.
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What are the functions of the vW protein?
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+ Carrier & stabilizing protein for FACTOR VIII coagulation molecule
+ Supports platelet adhesion and aggregation in primary hemostasis. |
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Clinical features of vWD:
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Variable presentation of clinical symptoms btw individuals and not all have symptoms due to 60% penetrance:
+ Mucosal bleeding + Cutaneous bleeding + Petechiae (Bruising, nose bleeds, GI and GU bleeds, menorrhagia) |
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What are the lab tests done for von Willebrand Disease?
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+ Measure vW protein
+ Functional activity - vWF:Ag and vWF:RCoF + Evaulate factor VIII activity + REPEAT TESTING IS RECOMMENDED BECAUSE FIRST SET OF TESTS MAY BE NORMAL + Factors assoc. with variation in tests: age, thyroid hormones, estrogen hormone levels and blood type. |
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Which blood type have the lowest levels of vWF:Ag?
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Blood type O - 75%
Blood type AB have mean levels of about 123% |
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vWD is classified into three subtypes:
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I & III - Quantitative abnormalities in the vW proteins
II - Qualitative abnormality |
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Which of the three subtypes of vWD has the following char:
+ Quantitative abnormalities + Most difficult to treat + The three factors in vWD testing may be at * borderline* |
Type I
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Which of the three subtypes of vWD has the following char:
+ Disceprancy in values from all three assays of vWD. + If vW protein is normal and enough, then there is correlation of VIII coagulant activity. + If vW protein is dysfuntional, Ristocetin cofactor activity will be disproportionately wrong. |
Type IIA and Type IIB hemophiliacs.
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Which of the three subtypes of vWD has the following char:
+ Increased affinity of the vW protein for platelet glycoprotein Ib. + May have low platelet count |
Type IIB vWD
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This vWD subtype has disproportionately low factor VIII, mimicks hemophilia A:
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Type 2N
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Multimer analysis of vWD protein separates protein multimers of differnt sizes. What patients may be classified by looking at these results:
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Type II
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Which inherited coagulated disorder is common in the Jewish population and should be screened in this group of patients:
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Factor XI deficiency - hemophilia C
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List some of the acquired coagulation disorders:
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Acquired inhibitors
Disseminated Intravascular coagulation Vitamin K deficiency Liver disease and bleeding |
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What are the common acquired inhibitors associated with bleeding disorders?
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IgG ab against factor VIII, mostly post partum, rheumatology or lymphoproliferative disorder
ab againts vW factor protein - have prolonged PTT and easily misdiagnosed as as acquired hemophilia. ab to factor V, sually associated with thrombin glue. Have progressivly prol. PT and PTT. Don't respond to vitamin K. |
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Name some of the common causes of DIC:
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Septicemia
Malignancies Hemolytic transfusion rxns Obstetric disorders -retained dead fetus, amniotic embolism, abruptio placents. |
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Clinical manifestations of DIC:
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Main process triggering DIC
Bleeding Purpuric lesions Organ failure due to deposition of fibrin in different tissues. |
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Lab. findings of DIC:
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Thrombocytopenia - due to platelet consumption
RBC fragmentation within blood vessels Decreased fibrinogen High D-D dimer levels due to fibrin degredation Low factor V Prolonged PT and PTT |
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How would you manage DIC?
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Treat cause
Replace clotting factors In chronic DIC - judicious use of anticoagulants may improve clinical and lab findings but usually not due to risk of bleeding. |
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What group of people are likely to present with hemorrhagic disorders due to vitamin K deficiency?
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Newborns. - hemorrhagic disease of the newborn.
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Clinical manifestations of vitamin K deficiency:
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Prolonged PT and PTT
Fibrinogen level and thrombin time is normal Platelet count is normal. |
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Clinical manifestations of Liver disease:
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PT prolonged prior to PTT
Thrombocytopenia - due to portal htn and splenomegaly linked to liver disease. ** decreased ability to synthesize coagulation proteins, first ones affected are those in extrinsic (VII) -->and common coag. pathway (II, X, V, IX) ** FACTOR VIII IS NOT AFFECTED IN LIVER DISEASE |
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What etiologies cause prolonged PT?
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Factor VII deficiency
Fibrinogen abnormality Early liver disease Early vitamin K deficiency Early warfarin effect Early DIC Lupus anticoagulant |
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What etiologies cause prolonged PTT?
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Factor VIII deficiency
Factor IX deficiency Factor XI deficiency Factor XII deficiency Heparin Lupus anticoagulant |
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What etiologies cause prolonged PT/PTT?
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Fibrinogen
Factor II deficiency Factor V deficiency Factor X deficiency liver disease Vitamin K deficiency Warfarin therapy |
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What etiologies have normal PT/PTT?
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vWD
Factor XIII deficiency Deficiency of alpha-2 antiplasmin |
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Inherited bleeding disorders:
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Hemophilia A and B
Von Willebrand disease Platelet dysfunction Factor XI deficiency Deficiency of factors V, VII and X and fibrinogen |
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What components are needed both in vivo and in vitro for clot formation?
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--> Plasma proteins
--> Phospholipid --> Calcium |
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What information can be obtained by the thrombin time and which drug inhibits this?
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Where thrombin is placed in test tube and is used to get a direct measure of the ability of thrombin to clot fibrinogen.
Get an abnormal thrombin time with abnormal fibrinogen or administration of heparin |
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TRUE OR FALSE
Patients with disfibrinogenemia can bleed and clot at the same time. |
TRUE:
This fibrinogen that is 'disfigured' may clump and form clots. |
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Name the substrates of thrombin:
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Fibrinogen
Factor V Factor VIII Protein C |
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Factor VIII cofactor to IXa and its deficiency is known as:
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Hemophilia A
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Deficiency of factor IX is called:
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Hemophilia B
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Factor IX and VIII are contained on chromosome:
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Chromosome X
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TRUE OR FALSE
Women carriers of X-mutations of hemophilia can have hemopholia but at lower levels: |
TRUE
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What is the level of activity of the factors need for coagulation in patients with:
Mild Moderate Severe hemophilia ? |
Mild - 5 -50%
Moderate - 1-5% Severe hemophilia <1% |
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How do we diagnose hemophilia A or B?
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Clinical presentation
Prolonged aPTT Check to see which factors are affected: VIII or IX |
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Lyon's hypothesis:
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All X chromosomes in excess are inactivated in a random process.
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Name the major hormone augmenting megakaryocyte and platelet production:
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Thrombopoietin
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How are the Thrombopoitein levels in the following cases:
+ Increased platelet # + Decreased platelet # + Platelet destruction states: |
+ Increased platelet # -> Low TPO levels
+ Decreased platelet # -> High TPO levels + Platelet destruction states: Low - normal |
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What is the lifespan of platelets?
**** MUI IMPORTANTE **** |
9-10 days
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Both arterial and venous hemostasis involve coagulation factors, anticoagulants and fibrinolysis. Which of the two would you treat with antiplatelets and which would you treat with anti-fibrin?
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Venous: Platelet poor and fibrin rich, therefore treat with anti-fibrin
Arterial: Platelet rich - treat with anti-platelet |
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Why is a healthy endothelium the best antithrombus?
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Physical barrier to thrombogenic subendothelium
Expresses anticoagulants Has receptors for anticoagulant Lacks receptors for clotting factors Secretes platelet inhibitors |
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What kind of bleeding is evident in platelet disorders
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Mucocutaneous bleeding: gingival bleeding, menorrhagia, nose bleeding
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