coagulation disorders Flashcards
single factor deficiencies and anesthesia (treatment/replacement considerations)
tx of single factor deficiency depends on severity
for surgery, individual clotting factor levels of 20-25% provide adequate hemostasis
duration of effect for replacement therapy depends on turnover time of each factor
factor levels in different produces vary considerable
products available to treat single factor deficiencies
factor concentrates
recombinant factors
FFP
(take it, make it, or give them all)
______ml/kg of FFP is needed to obtain _____% increase in level of any clotting factor
15-20ml./kg
20-30% increase
coagulation disorders: hereditary deficiencies
hemophilia A
hemophilia B
vWB disease
coagulation DO’s: acquired deficiencies
vitamin K deficiency (from antibiotics, intestinal malabsorption, impaired nutrition) liver disease (parenchymal disease) DIC autoantibodies
congenital factor 8 deficiency: hemophilia A
factor 8 gene is a very large gene on the x chromosome
can be inherited or gene mutation
clinical severity is best correlated with factor 8 activity level
severe hemophilia
inversion or deletion of major portions
<1% factor VIII activity
diagnosed in childhood (spontaneous hemorrhage into joints, muscles, and vital organs)
requires factor VIII concentrates
mild hemophilia
6-30% factor VIII activity
may go undiagnosed until adulthood and undergoing major surgery
diagnosis of hemophilia A or B
prolonged aPTT, specific factor testing, and gene testing
anesthesia and hemophilia A
hematology consult
factor VIII level should be brought o at least >50% prior to surgery
FFP and cryo can also be used
consider TXA as adjunct
anesthesia and hemophilia A: mild hemophilia A tx
DDAVP 30-90 minutes prior to srugery
anesthesia and hemophilia A: moderate to severe hemophilia A
factor VIII concentrate
half life of FVIII is approximately 12 hours in adults (short as 6 hours in children)
may require replacement therapy for days to weeks after surgery
congenital F-IX deficiency: hemophilia B
similar clinical picture as hemophilia A
also x linked and much less common
factor 9 levels below 1% are associated with severe bleeding
mild disease often not detected until surgery or dental procedure (5-40%)
anesthesia and hemophilia B
similar to hemophilia A
hematology consult
replacement therapy
consider txa as adjunct
replacement therapy for hemophilia B
recombinant factor 9
purified factor 9
prothrombin complex concentrate (PCC’s) contain II, VII, IX, X (increased risk of thrombotic events, especially in orthopedic surgery)
factor 9 half life
18-24 hours. absorbed into collagen and vasculature
von willebrand disease
most common congenital bleeding disorder in the world. more prevalent in persons of european descent.
family of disorders caused by quantitative and/or qualitative defect
vWF role
mediates platelet adhesion and prolongs factor 8 half life. dual role in hemostasis, affecting both platelet function and coagulation.
- platelet adhesion (to vascular site of injury. platelets and G1b receptor)
- platelet aggregation (plt GIIb/IIIa receptor to platelet GIIb/IIIa receptor)
- carrier molecule for factor VIIII and cofactor for factor 9
v willebrand factor antigen
antigenic determinants on vWF measured by immunoassays, usually low in types 1 and 2, virtually absent in type 3
ristocetin cofactor activity (RCo)
functional assay of vWF activity based on platelet aggregation with ristocetin. reduced by the same degree as vWF:Ag in types 1 and 3, but to a greater extent in type 2 disease
where is vWF synthesized and stored
endothelial cells, platelets
vWF type 1
most common in 60-70% of patients
mild to moderate reduction in level of vWF
mild bleeding symptoms, easy bruising and nosebleeds
vWF type 2
9-30% of patients
qualitative defect of vWF
4 subtypes
vWF type 3
<1% of patients
nearly undetectable, severe quantitative phenotype
vWF platelet pseudo type
defect in platelets GIb receptor
what determines approach to treatment in vWF disease
specific type of disease and location and severity of bleeding
vWF type 1 first line of treatment
desmopressin test infusion
vWF type 1 second line of treatment if first line fails
intermediate or high purity virus activated factor VIII concentrates
vWF type 2 or 3 first line of treatment (and what to consider after for 1, 2, or 3)
intermediate or high purity virus activated factor VIII concentrates
transfusions of platelets could be required in special circumstances
what to monitor for intermediate or high purity virus inactivated factor 8 concentrates
factor VIII level, symptoms, vWF activity, vWF antigen.
replacement therapy goals in vWF disease: major surgery
maintain factor VIII level >50% for 1 week
prolonged Treatment in type 3 patients (> 7 days)
replacement therapy goals in vWF disease: minorsurgery
maintain factor VIII level >50% for 1-3 days
maintain factor VIII level >20%-30% for an additional 4-7 days
replacement therapy goals in vWF disease: dental extraction
single infusion to achieve factor VIII level >50% desmopressin prior to procedure for type 1
replacement therapy goals in vWF disease: spontaneous post traumatic bleeding
usually single transfusion of 20-40units/kg (of what?)
VIII
synonym
biologic half life
blood product source
anti hemophilic factor
12-15 hours
FFP, factor concentrates, cryoprecipitate
IX
synonym
biologic half life
blood product source
christmas factor
18-30
FFP, PCC, factor concentrates
DIC
thrombin does not stay at the site of vascular injury like normal. instead, thrombin is generated in response to an insulting factor (endotoxins, sepsis, amniotic fluid embolism)
leads to intravascular clotting
which then disseminates
blood clots form throughout the body causing end organ dysfunction
coagulation factors deplete and platelets are used up or become dysfunctional
fibrinolysis 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 microcirculation (IV sites, catheters, drains)
causes of DIC
sepsis (bacterial, viral, fungal) surrgery trauma cancer (more chronic, insidious onset, often leukemias) pregnancy complications (AFE, HELLP syndrome) snake bites (venom) frostbite burns transfusion reaction
acute DIC
processes of coagulation and fibrinolysis are dysregulated
widespread clotting with resulting bleeding
fibrin deposits as thrombosis in the circulation
depletion of platelets and clotting factors
regardless of the triggering event of FIC, once initiated, the pathophysiology of FIC is similar in all conditions
tissue factor
present in many cell surfaces (endothelial, macrophages, monocytes) and tissues (lung. brain, placenta). exposed and relapsed. binds with FVIIa and activates IX and X to form thrombin and fibrin in final common pathway
fibrinolysis
creates fibrin degradation products that inhibit platelet aggregation, have antithrombin activity, impair fibrin polymerization. all of which contribute to bleeding
paradoxical effect of fibrinolysis in setting of DIC
coagulation inhibitors are 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
lots and lots of clotting
depletion of platelets and clotting factors
fibrin degradation products (FDP)
excess and unregulated thrombin generation causes consumption of coagulation factors and increased fibrinolysis which in conjunction with platelet 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
blood tests in DIC
lab test abnormalities and clinical presentation of an underlying factor to help diagnose DIC
DIC panel (in isolation, they are not helpful)
low platelets but also platelet dysfunction
low fibrinogen
high INR and PT
high PTT
high D dimer (FDP) variable
TEGS and rotems
treatment of DIC
recognition
treat underlying condition (infection, abx. trauma, resuscitation, remove insult if possible)
supportive care (platelets, cryo, fibrinogen concentrate, FFP, heparin, TXA, PCC’s)
thrombin (DIC)
potent pro inflammatory protein and platelet aggregator
neutralizing thrombin effect is crucial
thrombomodulin
binds to thrombin and decreases pro inflammatory response- limited clinical trials
direct thrombin inhibitors
no RCTs yet
heparin
historically used in DIC with variable outcomes
reserved for early or highly prothrombotic states
high risk of additive bleeding
has been shown to reduce end organ dysfunction
often discontinued if/when overt bleeding starts
difficult to monitor because PTT is already prolonged due to coagulation factor consumption
TXA
in severe trauma, excessive thrombin is generated to rescue the host from excessive bleeding
simultaneously, plasmin is generated to breakdown the microvascular clots, but unfortunately is not able to isolate leading to widespread hemorrhage
early hyperfibrinolysis may be treated with TXA. consider single upfront bolus during acute period as later the balance is tipped toward thrombosis
CRASH-2 trial
prospective trials are still needed
hyperfibrinolysis management
txa, blood product support
procoagulant process is anticipated
once bleeding has been controlled, consider antocoagulatn treatment to control ongoing thrombin generation
in presenting procoagulant DIC, consider
anticoagulation first and blood product support for bleeding or invasive procedures. LMWH (thrombomodulin trial stages only)
blood product support for DIC includes
platelets, then cryo or fibrinogen concentrate, then FFP
