Chapter 38 - Hypercoagulable states

Question 1

Virchow’s triad

Answer 1

1) endothelial injury 2) stasis of blood 3) hypercoagulability

Question 2

Congenital hypercoagulable defects that increase both arterial and venous thrombosis

Answer 2

1) Hyperhomocysteinemia 2) increased lipoprotein A

Question 3

Patient risk factors for thrombosis

Answer 3

1) age 2) OC use 3) hormone replacement therapy 4) pregnancy 5) cancer 6) infection 7) trauma 8) surgery

Question 4

Two groups of congenital hypercoagulable states associated with VTE

Answer 4

1) reduced natural anticoagulants: antithrombin, protein C, protein S 2) defects resulting in gain of procoagulant function: factor V leiden, prothrombin G20210 mutation, increase coag factors 8, 9, 11 and dysfibrinogenemia group 2 less thrombogenic but more common

Question 5

Venous thromboembolism and inherited thrombophilias

Answer 5

TABLE 38.1

Question 6

Prevalence of protein C or S deficiency

Answer 6

< 1%

Question 7

Percentage of group 1 thrombophilia that will have symptomatic thrombotic event before 60 yo

Answer 7

30-50%

Question 8

Antithrombin deficiency prevalence

Answer 8

0.02% of population

Question 9

Three types of antithrombin deficiency

Answer 9

TYPE 1 = decrease antithrombin functional activity and antigen TYPE 2 = reduced activity but normal antigen levels; mutation in active inhibitory site TYPE 3 = moderate decreased activity due to impaired interaction with heparin

Question 10

Deficiency of protein C prevalence

Answer 10

0.2% 2.5-6% in people with VTE

Question 11

Action of activated protein C

Answer 11

Cleaves coagulant cofactor 8a and 5a

Question 12

Types of protein C deficiency

Answer 12

TYPE 1: reduced function and antigen protein level TYPE 2: reduced function but preserved antigen level

Question 13

Treatment of protein C deficiency

Answer 13

If VTE then consider lifelong anticoagulation especially if < 40 years

Question 14

Homozygous protein C deficiency get this neonatal disorder

Answer 14

Purpura fulminans

Question 15

Treatment of warfarin necrosis

Answer 15

1) FFP 2) vitamin K 3) heparin

Question 16

Protein S action

Answer 16

vitamin K-dependent cofactor for inactivation of factor 5a and 8a by activated protein C

Question 17

Types of protein S deficiency

Answer 17

TYPE 1: reduced function and antigen level TYPE 2: reduced function but normal antigen TYPE 3: reduced free protein S due to enhanced C4b binding but normal antigen

Question 18

Protein S forms in blood

Answer 18

20-40% free floating = active 60-80% bound to complement binding protein C4b

Question 19

Protein S level in pregnancy

Answer 19

Falls in 2nd and 3rd trimester

Question 20

Protein S level reduction associated with

Answer 20

1) cancer 2) lupus 3) antiphospholipid antibody syndrome (APLAS) 4) sepsis 5) chronic inflammatory disorder 6) advanced HIV

Question 21

Factor V leiden molecule pathology

Answer 21

1) mutation in 506 position 2) glycine for arginine 3) cleavage site to APC resistant

Question 22

Factor V Leiden epidemiology

Answer 22

2-7% European 10% of VTE patients 30-50% of patients being worked up for thrombophilia

Question 23

Other rare cleavage mutation of factor Va

Answer 23

Arg306Thr

Question 24

Prothrombin gene mutation G20210A key points

Answer 24

1) increased plasma level of prothrombin 2) increased prothrombin mRNA stability 3) most common in European population 1-4%; 5-10% of VTE patients, 15% of thrombophilia patients

Question 25

Ethnicity with highest factor 8 level

Answer 25

African american \> white and asian

Question 26

Measuring factor 8 activity key points

Answer 26

1) has to measure with ESR or CRP 2) each lab should define 90th percentile for population individually

Question 27

Factor 8 level significance

Answer 27

increases in inflammation infection, IBD, cancer

Question 28

Two metabolic pathways of homocysteine

Answer 28

1) vitamin B6 pathway = cystathionine beta synthase 2) folate, B12 pathway = 5,10-methylenetetrahydrofolatate reductase (MTHFR) and methionine synthase

Question 29

Effect of homocysteine on thrombosis

Answer 29

1) toxic effect on endothelium 2) enhanced platelet acdtivation 3) oxidation of LDL-C 4) inflammatory decrease in endothelial TM 5) increase in vWF and factor 8

Question 30

Lipoprotein A action

Answer 30

competes with tPA, plasminogen and plasmin for binding fibrin and endothelial annexin INHIBITS FIBRINOLYSIS

Question 31

Sticky platelet syndrome key points

Answer 31

1) autosomal dominant disorder 2) early onset MI and PAD 3) hyperactivity to epinephrine and ADP 4) normal response to thrombin, collagen and arachdonic acid

Question 32

Three types of platelet response in sticky platelet syndrome

Answer 32

TYPE 1: hyperactive to both ADP and epinephrine TYPE 2: hyperactive to epinephrine TYPE 3: hyperactive to ADP

Question 33

Treatment of sticky platelet syndrome

Answer 33

ASA

Question 34

Recurrence of VTE in unprovoked VTE

Answer 34

5-10% per year 50% develop by 10 years

Question 35

Acquired hypercoagulable states

Answer 35

1) APLAS 2) cancer 3) HIT 4) chronic inflammation (IBD, Behcet's, SLE) 5) surgery 6) pregnancy, estrogen 7) infection

Question 36

APLAS key points

Answer 36

1) can co-exist with SLE but 50% do not 2) antibodies against lupus anticoagulant 3) antibodies bind anticardiolipin and beta 2 glycoprotein

Question 37

Lupus anticoagulant and anti cardiolipin antibody effect

Answer 37

10x increase in VTE

Question 38

APLAS on coagulation test

Answer 38

prolonged aPTT

Question 39

Characteristic of APLAS

Answer 39

thrombosis at unusual sites recurrence 50% high mortality variant = CAPS

Question 40

Cancer on coagulation

Answer 40

increase fibrinogen, factor 8 and platelet VTE 1-43% risk of VTE 7-20x increase

Question 41

Nonbacterial thrombotic endocarditis

Answer 41

cardiac manifestation of systemic hemostatic activation in cancer patients = platelet and fibrin vegetation on cardiac valves 30-70% have lab evidence of overt DIC

Question 42

Pregnancy on coagulation factor changes

Answer 42

1) increase fibrinogen, factor 8 2) reduce protein S

Question 43

VTE risk in pregnancy

Answer 43

4-6x higher

Question 44

Rate of left sided VTE in pregnancy

Answer 44

90%

Question 45

Pregnant patients with these deficiency should get anticoag prophylaxis

Answer 45

1) antithrombin deficiency 2) protein C deficiency 3) protein S deficiency 4) antiphospholipid syndrome 5) factor V leiden

Question 46

Treatment of pregnant patient with active thrombosis

Answer 46

LMWH full dose

Question 47

HIT pathophysiology

Answer 47

Antibody against neoantigen on platelet factor 4 (PF4) after binding to heparin

Question 48

Thrombotic rate in HIT patients

Answer 48

30-70%

Question 49

Rate of thrombotic death in HIT

Answer 49

4-5%

Question 50

Monitoring platelets in HIT

Answer 50

1) 5 days after starting heparin 2) 50% decrease triggers investigation 3) serologic screening for HIT-associated heparin/PF4 antibody

Question 51

Algorithm to decide on testing or just treating new VTE patients

Answer 51

FIGURE 38.1

Question 52

Laboratory tests to order depending on family history

Answer 52

FIGURE 38.2

Question 53

Thrombophilic defects and tests available for testing

Answer 53

TABLE 38.2