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IHO Week 6 - WLB > Thrombotic Disorders - Krafts > Flashcards

Thrombotic Disorders - Krafts Flashcards

1
Q

What kind of blood flow increases the risk of thrombi?

A

Turbulent flow!

  • aneurysms
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2
Q

What does a thrombus look like microscopically?

A
  • organized cells
    • fibroblasts
    • some trapped inflammatory cells
    • small white spaces
  • can use elastin stain to tell where clot ends and vessel wall begins
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3
Q

What happens to a blood vessel after a thrombus forms?

A
  • Thrombus can propagate itself
    • add to itself in the direction of blood flow
  • Body able to resolve clot entirely
    • endogenous tPA breaks down fibrin
    • everything washes away
  • Part of thrombus breaks off and travels up to the next vessel and gets stuck
    • usually end up in small vessels of lung (PE)
  • Blood vessel can re-canalize to allow blood flow through, but thrombi remain present
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4
Q

What is the first arm of Virchow’s Triad of thrombosis risk factors?

A
  • Endothelial damage (anything that disrupts endothelium)
    • atherosclerosis
      • hypertension
      • hyperlipidemia
      • obesity
      • smoking
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5
Q

What is the second arm of Virchow’s Triad of thrombosis risk factors?

A
  • Stasis
    • immobilization (bed ridden)
    • varicose veins
    • cardiac dysfunction
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6
Q

What is the third arm of Virchow’s Triad of thrombosis risk factors?

A
  • Hypercoagulability
    • trauma/surgery
    • carcinoma
      • adenocarcinomas have mucin that kicks of the coag cascade
    • estrogen/postpartum
    • thrombotic disorders
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7
Q

What do you do if your patient has a clot?

A
  • Get a good history
    • risk factors
    • family Hx
  • Order routine lab tests
    • INR, PTT, TT
  • Start to worry if:
    • no obvious cause
    • family Hx
    • weird location (anywhere but deep veins of the leg)
    • recurrent (1+)
    • patient is young
    • miscarriages
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8
Q

What are the 6 Hereditary Thrombotic Disorders?

A
  • Factor V Leiden
  • ATIII deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Factor II gene mutation
  • Homocyteinemia
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9
Q

What characterizes Factor V Leiden?

A
  • Most common cause of unexplained thromboses
  • Point mutation in factor V gene
  • Factor V can’t be turned off
  • Need genetic testing for diagnosis
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10
Q

What is Factor V Leiden pathogenesis?

A
  • A mutated factor V gene
    • single point mutation
    • discovered in Leiden, Netherlands
  • Produces abnromal factor V
    • participates in the cascade normally
    • can’t be cleaved by protein C (due to change in structure)
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11
Q

How common is factor V Leiden?

A
  • Half of patients with unexplained thromboses!
  • 5% of Caucasians have it
  • VERY rare in non-Caucasians
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12
Q

What is the risk of getting a clot with Factor V Leidan mutation?

A
  • Heterozygotes: 7x normal
  • Homozygotes: 80x normal
  • Normal risk = 1-2 patients per 1000 (per year)
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13
Q

How do you diagnose Factor V Leiden?

A
  • Need genetic testing (PCR test for it)
    • PTT and INR are not helpful
      • pt can make fibrin at same rate
      • normal coags
      • do not measure ability to stop coag
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14
Q

How do you treat Factor V Leiden?

A
  • DON’T TREAT… unless there is a thrombosis
  • Then: given an anticoagulant for a while
  • If there are multiple episodes OR other risk factors
    • give Long-Term anticoagulation
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15
Q

What characterizes Antithrombin III Deficiency?

A
  • AT III is a natural anticoagulant
  • Potentiated by heparin
  • Lots of gene mutations exist
  • Very rare
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16
Q

What is antithrombin III?

A
  • Natural anticoagulant
  • Inhibits IIa, VIIa, IXa, Xa, XIa
  • Potentiated by heparin
17
Q

What is wrong with the ATIII gene in ATIII Deficiency?

A
  • Mutated gene produces less ATIII
  • Rara avis (<1%)
  • Lots of different mutations described
  • Can’t do genetic testing!
18
Q

What’s the risk of getting a clot with ATIII Deficiency?

A
  • Homozygotes: can’t survive
  • Heterozygotes: half get clots
  • Heparin won’t work
  • Antithrombin concentrates required
    • need all three anticoags (Protein S & C)
19
Q

What characterizes Protein C and S Defieciencies?

A
  • Proteins C and S are natural anticoagulants
  • C is also fibrinolytic and anti-inflammatory
  • Warfarin-induced skin necrosis
  • C deficiency rare; S deficiency super-rare
20
Q

What is Protein C?

A
  • Anticoagulant: inactivates Va and VIIIa
  • Fibrinolytic: promotes t-PA action
  • Anti-inflammatory: keeps cytokines low
21
Q

What is wrong with protein C gene in Protein C Deficiency?

A
  • Mutated gene produces less protein C
    • or defective protein C
  • Rara avis (<1%)
  • Lots of mutations described
  • Diagnosis: functional testing
22
Q

What is the risk of getting a clot with Protein C Deficiency?

A
  • Heterozygotes: 7x normal
  • Unique risks:
    • Warfarin-induced skin necrosis
    • Purpura fulminans
      • lesions of bleeding into skin
23
Q

When does Purpura Fulminans occur? Net result? Associated with?

A
  • Thrombotic state + vascular injury
  • Net result: skin necrosis
  • Associated with:
    • protein C and S deficiency
    • sepsis
24
Q

What is the treatment for purpura fulminans?

A
  • HARD TO TREAT
  • Usually in the setting of sepsis
  • May include administering protein C
25
Q

What characterizes Factor II Gene Mutation?

A
  • Factor II = prothrombin
  • Mutated gene makes too much prothrombin
    • Prothrombin itself is normal
  • Rare in non-Caucasians
26
Q

What’s wrong with the factor II gene? Result of mutation?

A
  • Mutated gene produces too much prothrombin!
    • Prothrombin itself is normal
  • 5% of caucasians (rare in others)
  • Clot risk: 2-20x normal
27
Q

What characterizes Hyperhomocysteinemia?

A
  • Homocysteine converts folate
  • Homocysteinuria = rare metabolic disorder
  • Too much homocysteine = thrombosis
  • Homocysteinemia has many causes
28
Q

What is Homocysteine?

A
  • Amino acid
  • Made from methionine
  • Maintains myelin
  • Converts dietary folate
29
Q

What is homocysteinuria?

A
  • rare metabolic disorder
  • deficient trans-sulphuration enzyme
  • increased homocysteine in blood, urine
  • increased thrombosis, premature atherosclerosis
30
Q

What is homocysteinemia?

A
  • Not so rare
  • MTHFR gene mutation
  • B12/folate deficiency
31
Q

Why is a build up of homocysteine bad?

A
  • Toxic to endothelium
    • forms ROS
  • Interferes with nitric oxide
    • NO is a vasodilater and an antithrombotic
32
Q

What is the risk of clotting in Homocysteinemia?

A
  • Heterozygous homocysteinemia
    • increased risk of thrombosis
    • premature atherosclerosis
    • Risk of venous thrombosis: 2.5x normal
    • Risk of arterial thrombosis: 10x normal
  • Homocysteinemia in B12/folate deficiency
    • Less worrisome
    • but watch out for other risk factors
33
Q

What characterizes Antiphospholipid Antibodies?

A
  • Autoantibodies against phospholipids
  • Falsely prolong INR
  • May cause thromboses
  • Antiphospholipid syndrome serious
    • multi-organ involvement
34
Q

What are antiphospholipid antibodies?

A
  • IgG antibodies against phospholipids
  • Three variants
    • anticardiolipin antibodies
    • lupus anticoagulants
    • antibodies against other molecules
35
Q

What do antiphospholipids antibodies do?

A
  • Bind to phospholipids (in vivo and in vitro)
  • Screw up coagulation tests:
    • bind up PTT/PT reagent
    • specimen can’t clot
    • test appears prolonged
  • Screw up other tests:
    • direct antiglobulin test
    • syphilis test
36
Q

Who develops antiphospholipid antibodies?

A
  • Children
    • infection
    • mild risk
  • Adults
    • autoimmune diseases
    • moderate risk
  • Elderly
    • drugs
    • no risk
37
Q

What is the effect of antiphospholipid antibodies in vivo vs. in vitro?

A
  • in vivo
    • promote coagulation
  • in vitro
    • inhibit coagulation
38
Q

What are the clinical findings in Antiphospholipid Antibody Syndrome?

A
  • Recurrent thrombosis
  • Recurrent spontaneous abortions
  • Increased risk of stroke
  • Pulmonary hypertension
  • Renal failure
39
Q

How do you detect antiphospholipid antibodies?

A
  • Order a PTT
  • If prolonged, order a PTT mixing study
    • If the PTT corrects → something was missing in patient’s blood (factor)
    • If the PTT doesn’t correct→ something in the patient’s blood inhibited normal coagulation
  • If normal, antibody may still be present
    • order fancy tests

IHO Week 6 - WLB (8 decks)

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