Coagulation Disorders Flashcards
products available to treat single factor deficiencies
- factor concentrates
- recombinant factors
- FFP (15-20 mL/kg of FFP needed to obtain 20-30% increase in level of any clotting factor)
- gene therapy
hereditary deficiencies
- hemophilia A
- hemophilia B
- von Willebrand disease
acquired deficiencies
- vitamin K deficiency
- liver disease
- disseminated intravascular coagulation
- autoantibodies
hemophilia A
- congenital factor VIII deficiency
- Factor VIII gene is a large gene on the X chromosome
- 1:5,000 males
- inherited or gene mutation
- severity determined with factor VIII activity level
severe hemophilia A
- <1% factor VIII activity
- diagnosed in childhood
- spontaneous hemorrhage into joints, muscles, and vital organs
- requires factor VIII concentrates
mild hemophilia A
- 6-30% factor VIII activity
- may go undiagnosed until adulthood when they undergo major surgery
hemophilia A diagnosis
- prolonged aPTT
- specific factor testing
- gene testing
hemophilia A anesthetic implications
- hematology consult
- factor VIII levels brought to at least >50% prior to surgery
- mild hemophilia A - DDAVP 30-90 minutes prior to surgery
- moderate to severe hemophilia A - factor VIII concentrate; may need therapy for days-weeks after surgery
- FFP and cryo
- TXA as adjunct
DDAVP
increases release of vWF and remember it is buddies with factor VIII so increases that too!
half-life of FVIII
12 hours in adults
6 hours in kids
hemophilia B
- congenital factor IX deficiency
- similar to hemophilia A
- 1:30,000 males (x-linked but less common)
- Factor IX levels below 1% associated with severe bleeding
- mild disease (levels between 5-40%) often not detected until surgery or dental procedure
- called royal hemophilia (queen victoria)
diagnosis hemophilia B
- prolonged aPTT
- specific factor testing
- gene testing
hemophilia B anesthetic implications
- similar to hemophilia A
- hematology consult
- replacement therapy - recombinant factor IX, purified F-IX, prothrombin complex concentrated (PCCs contain II, VII, IX, X)
- continue replacement therapy
- consider TXA as adjunct
factor IX half-life
18-24 hours
von willebrand disease
- most common congenital bleeding disorder in the world
- family of disorders caused by quantitative and/or qualitative defect
von willebrand factor (vWF)
- large multimeric glycoprotein that is necessary for normal plt adhesion, normal bleeding time, and stabilization of F VIII
- mediates platelet adhesion and prolongs half life of factor VIII
what synthesizes ans stores vWF?
- endothelial cells
- platelets
vWF functions
- affects plt function and coagulation
- platelet adhesion
- platelet aggregation
- carrier molecule for factor VIII and cofactor for factor IX
von willebrand disease type 1
- most common 60-70% of patients
- mild-moderate reduction in level of vWF
- mild bleeding symptoms (easing bruising, nosebleeds)
von willebrand disease type 2
- 9-30% of patients
- qualitative defect of vWF
- 4 subtypes
von willebrand disease type 3
- <1% of patients
- nearly undetectable, severe quantitative phenotype
platelet pseudo type von willebrand disease
-defect in the platelet’s G1b receptor
von willebrand disease treatment
- determined by the specific type
- location
- severity of bleeding
major surgery + von willebrand disease
- maintain factor VIII level >/= 50% for one week
- prolonged treatment in type 3 patients (>7 days)
minor surgery + von willebrand disease
- maintain factor VIII level >/= 50% for 1-3 days
- maintain factor VIII level > 20-30% for an additional 4-7 days
dental extraction + von willebrand disease
- single infusion to achieve factor VIII level >50%
- DDAVP prior to procedure for type 1
spontaneous or post traumatic bleeding + von willebrand disease
-usually single infusion of 20-40 units/kg
factor VIII blood product source
- antihemophilic factor
- FFP, factor concentrates, cryo
factor IX blood product source
- christmas factor
- FFP, PCC, factor concentrates
Disseminated Intravascular Coagulation (DIC)
- thrombin generated in response to an insulting factor (like endotoxins in sepsis or amniotic fluid embolism)
- leads to intravascular clotting which then disseminates
- blood clots form throughout the body which causes end organ dysfunction
- coagulation factors deplete and platelets are used up or become dysfunctional
- fibrinolysis is also activated and results in bleeding
DIC symptoms
- related to widespread clot formation –> chest pain, SOB, leg pain, problems speaking or moving
- patients can present with either clotting, bleeding, or both
- hemorrhages occur simultaneously from distant sites while there is ongoing thrombosis in micriocirculation (IV sites, catheters, drains)
causes of DIC
- sepsis
- surgery
- trauma
- cancer (more chronic, insidious onset, often leukemia)
- pregnancy complications (amniotic fluid embolism, HELLP syndrome)
- snake bite (venom)
- frostbite
- burns
- transfusion reaction
acute DIC pathophysiology
- process of coagulation and fibrinolysis are dysregulated
- widespread clotting with resultant bleeding (fibrin deposits as thrombosis in the circulation + depletion of plts and clotting factors)
- regardless of triggering event, patho of DIC is similar
- tissue factor is present in many cell surfaces and tissues; it is exposed and released in DIC; binds with factor 7a and activates 9 + 10 to form thrombin and fibrin in the final common pathway
fibrinolysis
- creates fibrin degradation products that will –> inhibit platelet aggregation, have antithrombin activity, impair fibrin polymerization
- all of the above contribute to bleeding
paradoxical effect in DIC
- coagulation inhibitors also consumed
- decreased inhibitor levels will permit more clotting
- increased clotting leads to more clotting
- thrombocytopenia occurs due to platelet consumption
- dysfunctional platelets occur due to inflammatory processes
thrombin excess in DIC
- lots and lots of clotting
- leads to depletion of platelets and clotting factors
- leads to fibrin degradation products
- excess and unregulated thrombin generation causes consumption of coagulation factors and increased fibrinolysis which in conjunction with plt dysfunction can lead to bleeding
- consumption of anticoagulant proteins with high antifibrinolytic activity and platelet aggregation also induced by thrombin can lead to thrombotic complications
DIC panel
- labs in isolation are not helpful, have to be seen together
- low platelets (93% of cases, but also plt dysfunction)
- low fibrinogen
- high INR and PT
- high PTT
- high D-dimer (FDP)
other DIC labs
- TEG
- ROTEM
treatment of DIC
- recognition
- treat underlying cause
- supportive - platelets, cryo, fibrinogen concentrate, FFP, heparin, TXA, PCCs
thrombin
- a potent proinflammatory protein and platelet aggregator
- neutralizing thrombin effect is crucial
- thrombomodulin binds to thrombin and decreases the proinflammatory response (limited to clinical trials)
- direct thrombin inhibitors (no RCTs yet)
heparin
- historically used in DIC with varied outcomes
- reserved for early or highly prothrombotic states
- high risk of additive bleeding
- has been shown to reduce end organ dysfunction
- often D/C if or when overt bleeding starts
- difficult to monitor because PTT is already prolonged due to coagulation factor consumption
TXA (tranexamic acid)
- in severe trauma, excessive thrombin is generated to rescue the host from excessive bleeding
- plasmin simultanesously generated to breakdown the microvascular clots, but unfortunately not able to isolate leading to widespread hemorrhage
- early hyperfibrinolysis may be treated with TXA
- CRASH 2 trial
