Coagulation Disorders Flashcards

1
Q

products available to treat single factor deficiencies

A
  • 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
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2
Q

hereditary deficiencies

A
  • hemophilia A
  • hemophilia B
  • von Willebrand disease
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3
Q

acquired deficiencies

A
  • vitamin K deficiency
  • liver disease
  • disseminated intravascular coagulation
  • autoantibodies
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4
Q

hemophilia A

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
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5
Q

severe hemophilia A

A
  • <1% factor VIII activity
  • diagnosed in childhood
  • spontaneous hemorrhage into joints, muscles, and vital organs
  • requires factor VIII concentrates
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6
Q

mild hemophilia A

A
  • 6-30% factor VIII activity

- may go undiagnosed until adulthood when they undergo major surgery

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7
Q

hemophilia A diagnosis

A
  • prolonged aPTT
  • specific factor testing
  • gene testing
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8
Q

hemophilia A anesthetic implications

A
  • 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
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9
Q

DDAVP

A

increases release of vWF and remember it is buddies with factor VIII so increases that too!

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10
Q

half-life of FVIII

A

12 hours in adults

6 hours in kids

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11
Q

hemophilia B

A
  • 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)
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12
Q

diagnosis hemophilia B

A
  • prolonged aPTT
  • specific factor testing
  • gene testing
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13
Q

hemophilia B anesthetic implications

A
  • 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
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14
Q

factor IX half-life

A

18-24 hours

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15
Q

von willebrand disease

A
  • most common congenital bleeding disorder in the world

- family of disorders caused by quantitative and/or qualitative defect

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16
Q

von willebrand factor (vWF)

A
  • 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
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17
Q

what synthesizes ans stores vWF?

A
  • endothelial cells

- platelets

18
Q

vWF functions

A
  • affects plt function and coagulation
  • platelet adhesion
  • platelet aggregation
  • carrier molecule for factor VIII and cofactor for factor IX
19
Q

von willebrand disease type 1

A
  • most common 60-70% of patients
  • mild-moderate reduction in level of vWF
  • mild bleeding symptoms (easing bruising, nosebleeds)
20
Q

von willebrand disease type 2

A
  • 9-30% of patients
  • qualitative defect of vWF
  • 4 subtypes
21
Q

von willebrand disease type 3

A
  • <1% of patients

- nearly undetectable, severe quantitative phenotype

22
Q

platelet pseudo type von willebrand disease

A

-defect in the platelet’s G1b receptor

23
Q

von willebrand disease treatment

A
  • determined by the specific type
  • location
  • severity of bleeding
24
Q

major surgery + von willebrand disease

A
  • maintain factor VIII level >/= 50% for one week

- prolonged treatment in type 3 patients (>7 days)

25
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
26
dental extraction + von willebrand disease
- single infusion to achieve factor VIII level >50% | - DDAVP prior to procedure for type 1
27
spontaneous or post traumatic bleeding + von willebrand disease
-usually single infusion of 20-40 units/kg
28
factor VIII blood product source
- antihemophilic factor | - FFP, factor concentrates, cryo
29
factor IX blood product source
- christmas factor | - FFP, PCC, factor concentrates
30
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
31
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)
32
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
33
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
34
fibrinolysis
- creates fibrin degradation products that will --> inhibit platelet aggregation, have antithrombin activity, impair fibrin polymerization - all of the above contribute to bleeding
35
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
36
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
37
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)
38
other DIC labs
- TEG | - ROTEM
39
treatment of DIC
- recognition - treat underlying cause - supportive - platelets, cryo, fibrinogen concentrate, FFP, heparin, TXA, PCCs
40
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)
41
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
42
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