Bleeding and Clotting Disorders

Question 1

Intrinsic Pathway
Starts with factor ___
Tested by:

Answer 1

12

PTT (Partial thromboplastin time) or APTT

Question 2

Extrinsic Pathway
Start at factor ___
Tested by:

Answer 2

7

prothrombin time

Question 3

Prothrombin time prolonged by deficiencies in: (5)

Answer 3

Factor 7, 10, 5
Prothrombin (II)
Fibrinogen (I)

Question 4

International Normalized Ratio (INR)

Answer 4

Standardize method developed to compensate for variation among reagent and instrument systems in prothrombin time.

Question 5

PTT prolonged by deficiencies in:

Answer 5

any plasma clotting factor except 7 or 13

Question 6

Most common inherited deficiencies associated with bleeding with prolonged PTT

Answer 6

Factor 8, Factor 9

Question 7

Specific factor inhibitor associated w/ ____ which leads to ____. Causes prolonged ___

Answer 7

antibody to factor 8
severe bleeding diathesis
PTT

Question 8

Deficiency associated with long PTT w/o risk of bleeding

Answer 8

Factor 12

Question 9

Antiphospholipid antibody:
Prolonged ___
Cause:

Answer 9

Antibodies against phospholipid protein complexes
PTT
Paradoxically: hypercoagulatibility, thrombosis

Question 10

PT and PTT prolonged seen in:

Answer 10

Common pathway deficiency

Multiple factor decificiencies

Question 11

PT prolonged, normal PTT seen in:

Answer 11

Factor 7 deficiency

Question 12

PTT prolonged, normal PT seen in:

Answer 12

Factor 8, 9, 11, 12 deficiency

Question 13

Mixing study: Correction of PT or PTT to normal suggests:

Answer 13

Factor deficiency

Question 14

Mixing study: Test remains prolong suggest:

Answer 14

inhibitor, antibody

Question 15

D-dimer increased when:

Evaluates:

Answer 15

Increased fibronolysis –> excessive generation of products of digestion of fibrin by plasmin
DVT, disseminated intravascular coagulation, PE

Question 16

Platelet function analysis (PFA-100) used to:

2 tests:

Answer 16

assess how effectively platelets work to close hole in membrane
Collagen/Epinepherine
Collagen/ADP

Question 17

Long closure time w/ Col/Epi, normal Col/ADP caused by:

Answer 17

Drugs (aspirin, NSAIDS)

Question 18

Long closure time w/ Col/Epi and Col/ADP caused by:

Answer 18

Qualitative platelet disorders
Von Willebrand disease
Thrombocytopenia
Anemia

Question 19

____ more likely to cause mucocutaneous bleeding (epistaxis, menorrhagia, pectechia) than hematomas

Answer 19

Platelet abnormalities

Question 20

Thrombocytopenia =

Answer 20

decrease in number of platelets in peripheral circulation

Question 21

Mechanisms of causing thrombocytopenia:

Answer 21

Decreased platelet production
Splenic sequestration
Increased peripheral destruction of platelets

Question 22

Increased peripheral destruction of platelets causes
Non-immune destruction:

Immune destruction:

Answer 22

1. Disseminated intravascular coagulation
2. Microangiopathic hemolytic anemia: vasculitis
3. Alloimmune destruction: maternal fetal incompatibility, after blood transfusion
4. Drug inducted: absorption of drug on platelet surface –> ab formation –> platelet removed in liver and spleen
   Quinine
   Heparin: ab directed against heparin and platelet factor 4 –> platelet aggregation

Question 23

Acute immune thrombocytopenic purpura=
Typically in: (age, sex)
Associated w/:
Treatment:

Answer 23

Acute onset w/ severe thrombocytopenia

2-6 y/o, both M and F

Viral infection: cross reactivity of ab b/w viral infection and platelets

Steroids, IVIG, Rh immune globulin

Question 24

Chronic immune thrombocytopenic purpura =
Typically in: (age, sex)
Associated with:
Treatment:

Answer 24

Not as severe thrombocytopenia. Insidious onset w/ remissions and relapses

20-40 y/o, F

Other autoimmune disorders

Steroids, splenectomy, Rituximab

Question 25

Clinical presentation of thrombotic thrombocytopenic purpura (5)

Answer 25

``` Thrombocytopenia Microangiopathic hemolytic anemia Neurologic symptoms Fever Renal insufficiency ```

Question 26

Thrombotic thrombocytopenic purpura = Etiology: Treatment:

Answer 26

Deposition of platelet thrombi in small vessels --> schistocytes in peripheral blood Deficiency of protease ADAMTS13 that cleaves von Willebrand multimers --> aggretate platelets --> deposit of thrombi Plasmapheresis

Question 27

Drugs that induce platelet disorders:

Answer 27

Aspirin, indomethacin, NSAIDs | Clopidogrel (Plavix): block ADP receptor on platelets

Question 28

``` Hemophilia A = deficiency of ____ Genetics: Clinical manifestation: Lab evaluation: Treatment: ```

Answer 28

Factor 8 Sex-linked: inversion mutation of X chromosome Delayed bleeding from small wounds Bleeding into joints, hematomas, hematuria Joint destruction, muscle atrophy Prolonged PTT, normal PT Factor assay Factor replacement

Question 29

``` Hemophilia B = deficiency of ___ Genetics: Clinical manifestation: Lab evaluation: Treatment: ```

Answer 29

Factor 9 Sex-linked: point mutation Mild hemophilia Prolonged PTT, normal PT Factor assays Recombinant factor 9 replacement

Question 30

Factor 12 deficiency

Answer 30

Rare, benign | Increase PTT but no increase risk of bleeding

Question 31

``` Von Willebrand Disease = Genetics: Symptoms: Lab evaluations: Treatment: ```

Answer 31

Plasma deficiency of von Willebrand factor Autosomal dominant Mucocutaneous bleeding: epistaxis, menorrhagia, easy bruising Long closure time by PFA Decreased vW antigenic level and activity Decrease Factor 8 Desmopressin: release vWF from endothelial cells vWf replacement

Question 32

Subtypes of Von Willebrand Disease:

Answer 32

Type 1: most common: mild-moderate quantitative decrease in vWf Type 2: qualitative defect in vWF Type 3: rare: severe quantitative deficiency of vWf. Autosomal recessive. No factor 8 at all.

Question 33

``` Liver disease lab values: PT, PTT: FDPs, D-Dimers: Fibrinogen: Platelet count: Factor 8 ```

Answer 33

``` Increase PT, PTT Increased FDP, D-Dimer Decreased fibrinogen Decreased platelet count Increased factor 8: activated endothelial cells ```

Question 34

Disseminated Intravascular Coagulation = Coagulation factors level: Inhibitors of coagulation level: End result:

Answer 34

Extensive intravascular thrombin formation --> deposition of fibrin in microvasculature and thrombosis of small and medium sized vessels Depleted coag factors Inhibitors (antithrombin 3, protein C and S) consume and fail to control coagulation process Ischemic tissue injury Hemorrhage: consumption of clotting factors

Question 35

2 mechanisms for triggering acute DIC

Answer 35

Widespread release of tissue factor into blood | Widespread injury to endothelial cells

Question 36

``` Lab values of DIC PT, PTT: FDPs, D-Dimers: Fibrinogen: Platelet count: Smear: ```

Answer 36

``` Increased PT, PTT Increased FDPs, D-dimers: increased fibrinolysis Decreased fibrinogen: consumption Decreased platelet: consumption Fragmented RBCs ```

Question 37

Most common cause of acquired thrombophilia that can be tested

Answer 37

Antiphospholipid antibody syndrome

Question 38

Antiphospholipid antibody syndrome = Associated w/: (3) Labs:

Answer 38

Development of ab against plasma proteins w/ affinity for anionic phospholipids Acquired thrombophilia 1. Venous and arterial thrombosis 2. Recurrent fetal loss 3. Thrombocytopenia Prolonged PTT Presence of lupus anticoagulant

Question 39

Factor V Leiden =

Answer 39

Inherited thrombophilia Factor V can't be cleaved by activated Protein C Increased levels of factor V

Question 40

Prothrombin gene mutation =

Answer 40

inherited thrombophilia Mutation of G20210A