Hemostasis / Thrombosis Flashcards
which clotting factor deficiency is not associated with a bleeding tendency?
factor XII (12)
What 2 factors associated with severe bleeding in heterozygous state?
FXI and FVII deficiencies
What is the treatment for FV & fibrinolytic factor deficiencies?
FFP
What is the treatment of FII and X deficiencies?
Prothrombin complex concentrates(PCC)
What is the treatment of FXIII and fibrinogen disorders?
Purified concentrates(FXIII and fibrinogen) or cryoprecipitate when concentrates not available
What happen to fibrinogen when both PT and aPTT are prolonged?
Fibrinogen will be reduced or abnormal
When thrombin time prolonged?
When fibrinogen is reduced or abnormal, in presence of inhibitors, presence of thrombin inhibiting drugs and hypoalbuminemia.
What clotting factor deficiencies suspected if aPTT normalized in mixing studies?
FXII, FXI, FIX & FVIII
If PT normalized in mixing study what factor deficiencies?
FVII
If both PT and aPTT normalized in mixing studies?
FX, FV, FII and fibrinogen
What is the screening test for FXIII deficiency?
Urea clot lysis assay except in newborn period may give false positive result and mild deficiencies better to use functional FXIII assays ( FXIII activity, antigen and FXIII A and B subunit)
Where is vWF synthesized?
Megakaryocytes and endothelial cells
What is the important of desmopressin(DDAVP) for vWF?
It induce the release of vWF from storage sites into plasma
What bleeding disorder suspected with MSK bleed
Fibrinogen disorder, FX,FII and FXIII deficiencies
What bleeding disorder common with GI and CNS bleeds?
FX deficiency
What bleeding disorder suspected with umbilical cord bleed
Fibrinogen, FII, V, XIII deficiencies
virchow’s triad
stasis
endothelial damage
hypercoagulability
peds age groups at highest risk of thrombosis
newborns
adolescents
what is the cause of purpura fulminans?
homozygous deficiency of protein C and/or S
where are protein C and S made?
liver
what are the antiphospholipid antibodies?
- lupus anticoagulant
- anti-cardiolipin antibodies
- anti-beta-2-glycoprotein I (beta2-GPI) antibodies
definition of antiphospholipid syndrome
The presence of thrombosis or pregnancy loss with the persistent (2 tests performed 12 weeks apart) presence of APLA (LAC or ACLA or B2-GPI)
what should you check in patients with MTHFR gene polymorphisms?
homocysteine level - if elevated, may be at increased risk of clot
who should have thrombophilia testing
- unprovoked VTE
- recurrent VTE
- purpura fulminans
- fam hx of thrombophilia (may provide anticipitory guidance about starting prothrombotic meds etc)
management of a child who you suspect has purpura fulminans
- test for protein C and S
- FFP 10-20ml/kg Q6-12 hr
how to manage blocked CVC that needs removal
anticoagulation x 3-5 days prior to removal to minimize risk of embolization
if a child presents with a PE, what should you look for?
DVT - 50% have extremity clot
why does leukemia increase risk of thrombosis
increased thrombin generation
what platelet counts are recommended for patients on anticoagulation?
> 50 for treatment
> 30 for prophylaxis
three signs of RVT
- thrombocytopenia
- palpable flank mass
- hematuria
patients that may not respond to treatment with unfractionated heparin
those with antithrombin (FII) deficiency
how does unfractionated heparin work
binds and potentiates the effect of anti-thrombin
pathophysiology of warfarin induced skin necrosis
acquired protein c deficiency
vitamin K dependent coagulation factors
factor 2, 7, 9, 10 and protein C
UFH target anti-Xa levels
- 35-0.7 (aPTT 60-85 s)
- should use PTT when you have hyperbilirubinemia
LMWH target anti-Xa levels
0.5-1.0
target INR for mechanical valve
2.5-3.5
treatment of DVT without risk factors
anticoagulate 9-12 months
treatment of DVT with chronic risk factors
indefinite
treatment of DVT with acute risk factors
x3 months, then switch to prophylaxis if risk factors still present
what is warfarin induced skin necrosis
acquired protein C deficiency, occurs within 3-10 days of starting treatment with warfarin
how can you test for HIT?
ELISA for anti-platelet factor 4 antibodies (high sensitivity, low specificity)
components of the 4T score for HIT
- degree of thrombocytopenia < 50%, plts > 20
- timing of thrombocytopenia (5-10 days after starting heparin)
- presence of new thrombosis
- no other cause of thrombocytopenia
diagnostic criteria for anti-phospholipid antibody syndrome
Defined by the presence of vascular thrombosis or pregnancy loss with the persistent (2 tests performed 12 weeks apart) presence of APLA (LAC or ACLA or B2-GPI)
how do you test for a lupus anticoagulant? (3 steps)
- Demonstrating an abnormal aPTT
- Mixing study to show that it does not correct – due to presence of inhibitor
- Confirmatory test – add phospholipids to prove that the abnormality is phospholipid dependent
what is the INR
(patient’s PT/control PT)to the power of ISI, where ISI = international sensitivity index (sensitivity of thromboplastin)
list novel anticoagulants and their mechanism of action
Rivaroxaban/apixaban - oral factor Xa inhibitors
Dabigatran - oral direct thrombin inhibitor
reversal of warfarin - INR > 8 and significant bleeding
FFP, Prothrombin complex concentrates, recombinant factor VIIa
reversal of warfarin - INR > 8, no bleeding
vitamin K (PO or IV)
on what chromosome is vWF encoded?
chromosome 12
where is vWF made and stored?
endothelial cells (stored in weibel-palade bodies) and megakaryocytes (stored in alpha granules)
functions of vWF
- Platelet adhesion to injured endothelium via GPIb/IX and collagen
- To assist with platelet aggregation via GPIIb/IIIa receptor
- Carrier protein for F8 – protecting it from degradation by protein C
inheritance of vWD
Type 1, Type 2 A/B/M - autosomal dominant
Type 2N, Type 3 - AR
factors which affect vWF levels
- ABO blood type (lower levels in Type O)
- High estrogen states
- Hypothyroidism (decreases levels of vWF)
- Stress
- Acute illness
- DDAVP
VWF/F8 concentrates
Humate-P
Willate
Alphanate
Treatment options for VWD
- antifibrinolytics
- estrogens (OCP)
- DDAVP (Risk of hyponatremia, seizures - tachyphylaxis)
- VWF/factor 8 concentrates
- cryo
conditions associated with acquired VWD
- Wilms tumour
- Hypothyroid
- SLE
- Aortic stenosis
- LVAD
in what type of VWD is DDAVP contraindicated?
type 2B - can worsen thrombocytopenia
