bleeding disorders

Question 1

interpretation of mixing studies:

correction of the test at time point 0 and at 2 hours implies

Answer 1

correction of the test at time point 0 and at 2 hours implies that the patient has a clotting factor deficiency

Question 2

interpretation of mixing studies:

failure of the test to correct or a partial correction at 2 hours implies

Answer 2

failure of the test to correct or a partial correction at 2 hours implies that the patient has a circulating inhibitor protein (e.g. FVIII inhibitor, antiphospholipid antibodies, amyloid)

Question 3

quantitates factor activity levels

Answer 3

Factor Assay

Question 4

which factors are not measured by the PT or PTT

Answer 4

FXIII and the vWF:Ag

Question 5

measures the conversion of fibrinogen to fibrin

Answer 5

thrombin time

Question 6

thrombin time prolonged in (3)

Answer 6

1. afibrinoginemia- no or very low fibrinogen
2. dysfibrinoginemia- dysfunctional fibrin
3. fibrin- heparin

Question 7

von willebrand disease:

1. bleeding disorder
2. genetics
3. vWF levels in blood type
4. phenotype 1, 2 and 3

Answer 7

1. most common bleeding disorder
2. AD-variable penetrance and expression
3. vWF levels lowest in type O and highest in type AB
   phenotype:
   i. partiaal quantitative deficiency
   ii. qualitative defects of vWF
   iii. severe or complete deficiency of vWF and moderately severe factor VIII deficiency

Question 8

A large protein (850 - >10, 000 kDa) synthesized in endothelial cells (stored in Weibel-Palade bodies) and megakaryocytes (stored in platelet α granules)
It is assembled & circulates as multimers

Answer 8

vWF antigen

Question 9

vWF has two major functions:

Answer 9

1. mediated adhesion of platelets to endothelium

2. stabilizes FVIII in the circulation and as such has a role in blood coagulation

Question 10

Acquired vWD

1. autoantibodies
2. hypothyroidism
3. caridac
4. other

Answer 10

1. binding of vWF causes rapid clearance by the RES associated with SLE
2. decreased synthesis of vWF
3. destruction of vWF
4. drugs

Question 11

diagnosis of vWD (3)

Answer 11

1. Pt is normal and PTT often normal but can be prolonged
2. PFA-100 abnormal EPI and ADP
3. specific testing required

Question 12

diagnosis of vWD:

1. FVIII activity
2. vWF antigen
3. vWF functional assay

Answer 12

1. FVIII activity- low if vWF-ag low b/c vWF stabilizes FVIII in plasma
2. vWF antigen- normal range diffres w/ blood type
3. vWF functional assay- ristocetin cofactor assay (qualitative)

Question 13

treatment of vWD

6

Answer 13

1. DDAVP- desmopressin
2. factor VIII plus vWF concentrates
3. recombinant vWF concentrate
4. treat underlying condition in acquired vWD
5. Huma P
6. cryoprecipitate

Question 14

1. useful in Type 1 vWD
2. promotes release of stored vW-protein from the vascular endothelium
3. Raises vWF level 2- 3 fold but decreased effect with multiple use
4. is rarely used in type 2 subtypes, contraindicated in type 3

Answer 14

DDAVP- desmopressin

Question 15

1. replace vWF (e.g. Humate-P, Wilate, Alphanate)

2. required for Type 2, Type 3 and some Type 1 patient

Answer 15

factor VIII plus vWF concentrates

Question 16

adjunct for the treatment of vWD (3)

Answer 16

1. anti-fibrunolytic agent like epsilon aminocarpoic acid
2. estrogens that can increas the level of vWF
3. avoiding NSAIDS

Question 17

1. X linked recessive disorder (males are affected)
2. Carriers females can exhibit bleeding phenotype
3. Bleeding due to FVIII deficiency
4. Mutation are due to inversions, deletions, point mutations
5. 1:5000 live male births

Answer 17

Hemophilia A

Question 18

1. X linked recessive disorder (males are affected)
2. Carrier females can exhibit bleeding phenotype
3. Bleeding due to factor IX deficiency
4. Multiple mutations including deletions & point mutations
5. 1:25000 live births

Answer 18

Hemophilia B- Xmas dx.

Question 19

sites of recurrent hemarthroses with hypertrophy of synovial sheath over time and painful arthritis

Answer 19

target joints

Question 20

hemophilia

1. both characterized by
2. occur

Answer 20

1. characterized by spontaneous hemarthorses

2. occur w/in the first year of life

Question 21

1. Severe hemophilia: measured factor levels of ____; spontaneous and trauma related bleeding
2. Moderate hemophilia: factor levels of_____; bleeding with trauma and rare spontaneous bleeding
3. Mild hemophilia: factor levels of _____; bleeding with surgery and trauma, no spontaneous bleeding
4. Very mild hemophilia: factor levels of ____; bleeding with significant trauma

Answer 21

1. Severe hemophilia: measured factor levels of <1%; spontaneous and trauma related bleeding
2. Moderate hemophilia: factor levels of 1-5%; bleeding with trauma and rare spontaneous bleeding
3. Mild hemophilia: factor levels of 5- 25%; bleeding with surgery and trauma, no spontaneous bleeding
4. Very mild hemophilia: factor levels of 25-50%; bleeding with significant trauma

Question 22

diagnosis of hemophilia:

1. Pt
2. PTT
3. mixing studies
4. factor assay

Answer 22

1. Pt- normal
2. PTT- prolonged– FVIII and FIX
3. mixing studies- correction with 1:1 mix with normal plasma at both time 0 and at 2 hours
4. factor assay - quantify level of FVIII or FIX

Question 23

therapies for hemophilia

Answer 23

1. PRICE
2. antifibrinolytics
3. plasma derived- FVIII or FIX concentrates
4. recombinant - genetically engineered

Question 24

complications of hemophilia

Answer 24

1. artrhopathy
2. infections
3. inhibitors- neutralizad by high affinity IgG

Question 25

what is the goal of supression of inhibitors

Answer 25

desensitization – induce tolerance of the factor VIII or IX protein, stop production of the factor VIII or IX antibody

Question 26

bypass agents for patients with inhibitor issue used in acute hemorrhage

Answer 26

1. recombinant FVIIa and emicizumab-kxwh

Question 27

chronic management of hemophilia (3)

Answer 27

1. prophylactic therapy 2. on demand treatment- replacement factor for elective procedures and with bleeds 3. patient/family education

Question 28

hemophilia C 1. deficiency in 2. increased icidence in 3. variable 4. provoked usually 5. treatment

Answer 28

1. deficiency in FXI 2. increased incidence in Ashkenazi Jews 3. variable bleeding phenotype 4. provoked bleeding after dental work 5. treatment- Amicar or FFP/rFVIIa

Question 29

Acquired hemophilia: 1. ab to 2. occurs in 3. consequence 4. underlying disorder 5. treatment

Answer 29

1. ab to FVIII 2. 75% after age 50 3. death due to bleeding 4. underlying disorder: none> autoimmune disorder 5. treat underlying disorder, immunosupression

Question 30

thrombotic disorder that causes a consumptive coagulopathy | often resulting in hemorrhage, thrombosis, multi-organ failure

Answer 30

Disseminated Intravascular Coagulation

Question 31

DIC pathogenesis 1. known as 2. dysregulated thrombin generation leading to 3. platelets, coagulation factors, fibrinogen all show a 4. D-dimer 5. PT and PTT 6. treatment

Answer 31

1. known as microangiopathic hemolytic anemia 2. dysregulated thrombin generation leading to intravascular fibrin formation and secondary fibrinolysis 3. platelets, coagulation factors, fibrinogen all show a decrease 4. D-dimer is elevated 5. Pt and PTT are prolonged 6. manage bleeding patients and correct underlying disease

Question 32

hepatic cirrhosis is associated with severe coagulopathy

Answer 32

yep

Question 33

hemorrhagic disease of the newborn

Answer 33

it is due b/c the gut is relatively devoid of bacteria and the hepatocytes are immature ***Vitamin K is given IM to all newborns to prevent bleeding in the newborn period

Question 34

The bleeding time is a screening test which relies only on

Answer 34

integrity of blood vessels, platelet number and function and the von Willebrand factor.

Question 35

Schistocytes on the smear (microangiopathy) accompanied by low platelets, elevated PT and elevated PTT are the laboratory findings in

Answer 35

Disseminated Intravascular Coagulation (DIC)

Question 36

microangiopathy and thrombocytopenia but coagulation tests are normal

Answer 36

TTP (Thrombotic Thrombocytopenic Purpura) and HUS (Hemolytic Uremic Syndrome)