bleeding disorders Flashcards
interpretation of mixing studies:
correction of the test at time point 0 and at 2 hours implies
correction of the test at time point 0 and at 2 hours implies that the patient has a clotting factor deficiency
interpretation of mixing studies:
failure of the test to correct or a partial correction at 2 hours implies
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)
quantitates factor activity levels
Factor Assay
which factors are not measured by the PT or PTT
FXIII and the vWF:Ag
measures the conversion of fibrinogen to fibrin
thrombin time
thrombin time prolonged in (3)
- afibrinoginemia- no or very low fibrinogen
- dysfibrinoginemia- dysfunctional fibrin
- fibrin- heparin
von willebrand disease:
- bleeding disorder
- genetics
- vWF levels in blood type
- phenotype 1, 2 and 3
- most common bleeding disorder
- AD-variable penetrance and expression
- 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
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
vWF antigen
vWF has two major functions:
- mediated adhesion of platelets to endothelium
2. stabilizes FVIII in the circulation and as such has a role in blood coagulation
Acquired vWD
- autoantibodies
- hypothyroidism
- caridac
- other
- binding of vWF causes rapid clearance by the RES associated with SLE
- decreased synthesis of vWF
- destruction of vWF
- drugs
diagnosis of vWD (3)
- Pt is normal and PTT often normal but can be prolonged
- PFA-100 abnormal EPI and ADP
- specific testing required
diagnosis of vWD:
- FVIII activity
- vWF antigen
- vWF functional assay
- FVIII activity- low if vWF-ag low b/c vWF stabilizes FVIII in plasma
- vWF antigen- normal range diffres w/ blood type
- vWF functional assay- ristocetin cofactor assay (qualitative)
treatment of vWD
6
- DDAVP- desmopressin
- factor VIII plus vWF concentrates
- recombinant vWF concentrate
- treat underlying condition in acquired vWD
- Huma P
- cryoprecipitate
- useful in Type 1 vWD
- promotes release of stored vW-protein from the vascular endothelium
- Raises vWF level 2- 3 fold but decreased effect with multiple use
- is rarely used in type 2 subtypes, contraindicated in type 3
DDAVP- desmopressin
- replace vWF (e.g. Humate-P, Wilate, Alphanate)
2. required for Type 2, Type 3 and some Type 1 patient
factor VIII plus vWF concentrates
adjunct for the treatment of vWD (3)
- anti-fibrunolytic agent like epsilon aminocarpoic acid
- estrogens that can increas the level of vWF
- avoiding NSAIDS
- X linked recessive disorder (males are affected)
- Carriers females can exhibit bleeding phenotype
- Bleeding due to FVIII deficiency
- Mutation are due to inversions, deletions, point mutations
- 1:5000 live male births
Hemophilia A
- X linked recessive disorder (males are affected)
- Carrier females can exhibit bleeding phenotype
- Bleeding due to factor IX deficiency
- Multiple mutations including deletions & point mutations
- 1:25000 live births
Hemophilia B- Xmas dx.
sites of recurrent hemarthroses with hypertrophy of synovial sheath over time and painful arthritis
target joints
hemophilia
- both characterized by
- occur
- characterized by spontaneous hemarthorses
2. occur w/in the first year of life
- Severe hemophilia: measured factor levels of ____; spontaneous and trauma related bleeding
- Moderate hemophilia: factor levels of_____; bleeding with trauma and rare spontaneous bleeding
- Mild hemophilia: factor levels of _____; bleeding with surgery and trauma, no spontaneous bleeding
- Very mild hemophilia: factor levels of ____; bleeding with significant trauma
- Severe hemophilia: measured factor levels of <1%; spontaneous and trauma related bleeding
- Moderate hemophilia: factor levels of 1-5%; bleeding with trauma and rare spontaneous bleeding
- Mild hemophilia: factor levels of 5- 25%; bleeding with surgery and trauma, no spontaneous bleeding
- Very mild hemophilia: factor levels of 25-50%; bleeding with significant trauma
diagnosis of hemophilia:
- Pt
- PTT
- mixing studies
- factor assay
- Pt- normal
- PTT- prolonged– FVIII and FIX
- mixing studies- correction with 1:1 mix with normal plasma at both time 0 and at 2 hours
- factor assay - quantify level of FVIII or FIX
therapies for hemophilia
- PRICE
- antifibrinolytics
- plasma derived- FVIII or FIX concentrates
- recombinant - genetically engineered
complications of hemophilia
- artrhopathy
- infections
- inhibitors- neutralizad by high affinity IgG
what is the goal of supression of inhibitors
desensitization – induce tolerance of the factor VIII or IX protein, stop production of the factor VIII or IX antibody
bypass agents for patients with inhibitor issue used in acute hemorrhage
- recombinant FVIIa and emicizumab-kxwh
chronic management of hemophilia (3)
- prophylactic therapy
- on demand treatment- replacement factor for elective procedures and with bleeds
- patient/family education
hemophilia C
- deficiency in
- increased icidence in
- variable
- provoked usually
- treatment
- deficiency in FXI
- increased incidence in Ashkenazi Jews
- variable bleeding phenotype
- provoked bleeding after dental work
- treatment- Amicar or FFP/rFVIIa
Acquired hemophilia:
- ab to
- occurs in
- consequence
- underlying disorder
- treatment
- ab to FVIII
- 75% after age 50
- death due to bleeding
- underlying disorder: none> autoimmune disorder
- treat underlying disorder, immunosupression
thrombotic disorder that causes a consumptive coagulopathy
often resulting in hemorrhage, thrombosis, multi-organ failure
Disseminated Intravascular Coagulation
DIC pathogenesis
- known as
- dysregulated thrombin generation leading to
- platelets, coagulation factors, fibrinogen all show a
- D-dimer
- PT and PTT
- treatment
- known as microangiopathic hemolytic anemia
- dysregulated thrombin generation leading to intravascular fibrin formation and secondary fibrinolysis
- platelets, coagulation factors, fibrinogen all show a decrease
- D-dimer is elevated
- Pt and PTT are prolonged
- manage bleeding patients and correct underlying disease
hepatic cirrhosis is associated with severe coagulopathy
yep
hemorrhagic disease of the newborn
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
The bleeding time is a screening test which relies only on
integrity of blood vessels, platelet number and function and the von Willebrand factor.
Schistocytes on the smear (microangiopathy) accompanied by low platelets, elevated PT and elevated PTT are the laboratory findings in
Disseminated Intravascular Coagulation (DIC)
microangiopathy and thrombocytopenia but coagulation tests are normal
TTP (Thrombotic Thrombocytopenic Purpura) and HUS (Hemolytic Uremic Syndrome)
