Week 3: Coagulation Disorders Flashcards
What does the treatment of single-factor deficiency depend on?
the severity of the deficiency
For surgery what are the adequate individual clotting factor levels for hemostasis?
20-25%
What products are available to treat single factor deficiencies? (4)
factor concentrates
recombinants factors
FFP
gene therapy
What does the duration of the effect for replacement therapy depend on?
the turnover time of each factor
What are the three hereditary deficiencies?
hemophilia A
hemophilia B
Von Willebrand disease
What are the four acquired deficiencies?
vitamin K deficiency
liver disease
disseminated intravascular coagulation
autoantibodies
What factor is deficient in hemophilia A?
factor VIII
What is factor VIII?
gene is a very large gene on the X chromosome
Who does Hemophilia A affect?
1:5000 males
can be inherted or gene mutation
How is the clinical severity of hemophilia A determined?
best correlated with factor VIII activity level
What is severe hemophilia A?
<1% factor VIII activity
What is mild hemophilia A?
6-30% factor VIII activity
How do you diagnosis hemophilia A?
prolonged PTT, specific factor testing, and gene testing
For surgery, hemophilia A patients require
hematology consult
>50% factor VIII level
How do you treat mild hemophilia A prior to surgery?
DDAVP 30-90 minutes prior to surgery
How do treat moderate to severe hemophilia A prior to surgery?
factor VIII concentrate
may require replacement therapy for days to weeks after surgery
FFP and cryo
TXA as adjunct
What is the half life of Factor VIII in adults? pediatrics?
12 hours in adults
6 hours in peds
Hemophilia B is what factor deficiency?
Factor IX
Who does hemophilia B affect?
1:30,000 males (Xlinked and much less common)
What factor level for hemophilia B is associated with severe bleeding?
1%
What % factor levels of hemophilia B is mild disease?
levels between 5-40%
How do you diagnosis Hemophilia B?
prolonged aPTT, specific factor testing, and gene testing
WHo should be consulted before hemophilia B patients to go to surgery?
hematology consult
What is the replacement therapy for hemophilia B patients?
recombinant F IX
purified F-IX
prothrombin concentrate (PCCs) contain 2,9,10
What is the half life of factor IX?
18-24 hours
What is the most common congenital bleeding disorder in the world?
von willebrand disease
What is von willebrand disease?
a family of disorders caused by quantitative and/or qualitative defect
What does von willebrand factor do?
mediates platelets adhesion and prolongs factor VIII’s half life
Where is von willebrand factor stored and synthesized?
endothelial cells and platelets
What is the overall role of von willebrand factor?
dual role in hemostasis, affecting both platelet function and coagulation
What are the 3 specific roles of VWF?
platelet adhesion- vascular site of injury to PLT’s GIb receptor
Platelet aggregation- PLT GIIb/IIIa receptor to PLT GIIB/ IIIa receptor
carrier molecule for factor VIII and cofactor for factor IX
What is type 1 VWD?
mild-moderate reduction in level of vWF
mild bleeding symptoms- easy bruising, nosebleeds
What is the most common type of VWD?
type 1
What is type 2 VWD?
qualitative defects of vWF
4 subtypes
what is the % of type 2 vWD?
9-30% of patients
What is type 3 vWD?
nearly undetectable, severe quantitative phenotype
What is platelet-pseudo type wvd?
defect in platelet’s GIb receptor
what determines the treatment of vWD?
location and severity of bleeding
What are the replacement goals of major surgery with vWD patient?
maintain factor VIII levels >50% for 1 week
prolonged treatment in type 3 patients >7days
What are the replacements goals of minor surgery with vWD patient?
maintain factor VIII level >50% for 1-3 days
maintain factor VIII level >20%-30% for an additional 4-7 days
How would you treat a vWD patient for a dental extraction?
single infusion to achieve factor VIII level <50%
desmopressin prior to procedure for type 1
What is generated in response to an insulting factor during DIC?
thrombin
What is an insulting factor?
endotoxins in sepsis, amniotic fluid embolism
What does thrombin cause?
intravascular clotting then dissemination
What do the blood clots cause in DIC?
end-organ dysfunction
What is depleted or used up in DIC?
coagulation factors depleted and platelets are used up
What is activated in. DIC and results in bleeding?
fibrinolysis
what are the symptoms of DIC?
related to widespread clot formation
chest pain, shortness of breath, leg pain, problems with speaking or moving
patients can be clotting or bleeding or both
Where do hemorrhages occur during DIC?
they occur simultaneously from distant sites while there is ongoing thrombosis in the microcirulation
IV sites, catheters, drains
What are the 9 causes of DIC?
sepsis (bacterial, viral, fungal) surgery trauma cancer (more chronic) pregnancy complications (amniotic fluid embolism, HELLP syndrome) snake bites (venom) frostbite burns transfusion reaction
Acute DIC is
processes of coagulation and fibrinolysis are dysregulated
widespread clotting with resultant bleeding
what are the two processes that cause bleeding and clotting?
- fibrin deposits as thrombosis in the circulation
2. depletion of platelets and clotting factors
What is tissue factor?
present in many cell surfaces (endothelial macrophages, monocytes) and tissues (lung, brain, placenta)
What happens with tissue factor in DIC?
exposed and released
binds wit FVIIa and activates IX and X to form thrombin and fibrin in the common final pathway
Fibrinolysis creates a fibrin degradation products that cause what 3 things?
inhibit platelet aggregation
have antithrombin activity
impair fibrin polymerization
all contribute to bleeding
What is the paradoxical effect of acute DIC?
coagulation inhibitors are also consumed= more clotting
increased clotting leads to more clotting
thrombocytopenia occurs due to platelet consumption
dysfunctional platelets occur due to inflammatory processes
Thrombin allows for
depletion of platelets and clotting factors
fibrin degradation products
What does the excess and unregulated thrombin generation causes
consumption of coagulation factors and increased fibrinolysis which in conjunction with platelet dysfunction can lead to bleeding
What causes thrombotic complications?
consumption of anticoagulant proteins with high antifibrinolytic activity and platelet aggregation also induced by thrombin leads to complications
What labs diagnosis DIC?
DIC panel low platelets low fibrinogen high INR and PT high PTT HIgh D dimer TEGs and ROTEMs
How do you treat DIC?
recongition treat underlying conditions infection- give antibotics trauma- resuscitation, remove insult supportive- give platelets, cryo, fibrinogen concentration FFP heparin TXA (if in coagulation phase) PCCs (contain fewer natural anticoagulant than FFPs)
Thrombin is
a potent proinflammatory protein and platelet aggregator
Neutralizing what is crucial in acute DIC?
thrombin
Throbomodulin
binds to thrombin and decreases the pro-inflammatory response (limited clinical trials)
Direct thrombin inhibitors
no RCTs yet
Heparin in DIC
variable outcomes
reserved for early or highly prothrombotic states
high risk of additive bleeding
reduce end-organ dysfunction
discontinued if/when overt bleeding starts
difficult to monitor because PTT is already prolonged due to coagulation factor consumption
What is generated during severe trauma?
excessive thrombin to rescue the host from excessive bleeding
plasmin is also generated to breakdown the microvascular clots, but unfortunately is not able to isolate leading to widespread hemorrhage
What can tranexamic acid treat?
early hyperfibrinolysis
consider single upfront bolus during period as later the balance is tipped toward thrombosis
