Rav Hemo Kaplan Hypercoagulable States/ Thrombophilia

Front 1

how long to tx the p with
with transient risk factors for recurrent deep venous thrombosis.

Back 1

* A 3- to 6-month regimen is adequate anticoagulation

Front 2

before to start the lifelong anticoagulation what to do

Back 2

least two positive laboratory tests (anticardiolipin antibody or lupus inhibitor assay) at least 12 weeks apart should be documented to confirm the presence of an antiphospholipid antibody syndrome before a patient is committed to lifelong anticoagulation.

Front 3

inherited thrombophilic conditions, ..... is the most common

Back 3

factor V Leiden

Front 4

what mutation in prothrombin gene could lead to increased risk of DVT

Back 4

G→A mutation in the prothrombin gene at position 20210 (PTG20210A), resulting in higher prothrombin levels in affected individuals.

Front 5

Antithrombin (previously known as antithrombin III) deficiency

Back 5

Antithrombin (previously known as antithrombin III) deficiency is an autosomal-dominant disorder, and the prevalence of the heterozygous condition is 0.02% in the general population (homozygous antithrombin deficiency is generally not compatible with life). Antithrombin deficiency is associated with a risk for VTE of approximately 1% per year. Type 1 deficiency is a deficiency of the protein, whereas type II deficiency is characterized by a defective protein

Front 6

Protein C and protein S are

Back 6

Protein C and protein S are vitamin K–dependent proteins. Protein C requires activation by thrombomodulin-thrombin on the endothelial surface to neutralize factors VIIIa and Va, whereas protein S is a cofactor in this reaction.

Front 7

Protein C deficiency is inherited as

Back 7

Protein C deficiency is inherited as an autosomal-recessive trait, with 1 in 200 to 300 individuals affected, many of whom are asymptomatic.

Front 8

why the warfarin-induced skin necrosis could happen in some patients and how to prevemt

Back 8

Protein C has a half-life of approximately 6 hours, decreases to low levels soon after initiation of warfarin therapy, and is the cause of warfarin-induced skin necrosis in some patients. Concomitant treatment with heparin can prevent such an adverse event.

Front 9

Protein S deficiency is inherited as...
what happen in protein S and C deficiency

Back 9

Protein S deficiency is inherited as an autosomal-dominant trait.
Its frequency is less than that of protein C deficiency.
It circulates bound to C4b-binding protein, 40% of which is free and active.
Deficiencies of protein C, S, and antithrombin all lead to an increased risk for VTE
Arterial thrombotic events are rar

Front 10

Deficiencies of protein C, S, and antithrombin all lead to an increased risk for

Back 10

Deficiencies of protein C, S, and antithrombin all lead to an increased risk for VTE Arterial thrombotic events are rar

Front 11

Criteria for Diagnosis of Antiphospholipid Syndrome

Back 11

Vascular thromboses:
One or more episodes of a vascular thrombotic event.
2. Pregnancy morbidity:
One or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestation.
One or more premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia or severe preeclampsia or recognized features of placental insufficiency.
Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation.
Laboratory Criteria
1. Presence of lupus anticoagulant on two or more occasions at least 12 weeks apart.
2. Anticardiolipin antibody of IgG and or IgM isotype in medium or high titer on two or more occasions at least 12 weeks apart.
3. Presence of anti-β2-glycoprotein 1 antibody of IgG and or IgM isotype present on two or more occasions at least 12 weeks apart.

Front 12

Antiphospholipid Syndrome and pregnancy loss,

Back 12

strong correlation between this syndrome and pregnancy loss, presumably due to placental insufficiency in affected patients secondary to thrombosis

Front 13

antiphospholipid syndrome and a thromboembolic event, what tx

Back 13

long-term oral anticoagulant therapy

Front 14

when to test in the setting of acute thrombotic event

Back 14

weeks or months after it has occurred and when anticoagulant therapy has been discontinued, because active thrombosis may alter the level of some proteins.

Front 15

strongly thrombophilic patient is that who...
weak trombophilic patient is who...

Back 15

strongly thrombophilic : first idiopathic venous thrombosis before 50 years of age,
may have a history of recurrent thrombotic episodes,
and may have first-degree relative(s) in whom a documented thromboembolism has occurred before the age of 50 year

Weakly thrombophilic patients with a venous thromboembolism have none, or perhaps one, of these characteristics.

Front 16

Patients who are strongly thrombophilic should undergo testing for

Back 16

Patients who are strongly thrombophilic should undergo testing for activated protein C resistance, factor V Leiden, the prothrombin gene mutation, antiphospholipid antibodies, a lupus inhibitor, antithrombin deficiency, protein C deficiency, and protein S deficiency.

Front 17

Those who are weakly thrombophilic should undergo

Back 17

Those who are weakly thrombophilic should undergo either no special testing or testing for activated protein C resistance, factor V Leiden, the prothrombin gene mutation, antiphospholipid antibodies, and a lupus inhibitor. Testing for antithrombin deficiency, protein C deficiency, and protein S deficiency is not indicated in weakly thrombophilic patients.

Front 18

Antithrombotic Agents

Back 18

anticoagulants, antiplatelet agents, and thrombolytic or fibrinolytic agents

Front 19

difference between antithrombotic groups

Back 19

Thrombolytic - have a direct effect on thrombi by hastening their dissolution,
anticoagulants and antiplatelets -are always prophylactic because they prevent de novo initiation of thrombosis (primary prophylaxis) or extension or recurrence of established thrombi (secondary prophylaxis).

Front 20

Unfractionated Heparin

Back 20

Unfractionated heparin binds to antithrombin through a unique pentasaccharide in the heparin molecule,
enabling antithrombin to bind rapidly and neutralize the serine protease coagulation factors
(IIa, IXa, Xa, XIa, and XIIa)

Front 21

what is the reason for the frequent failure of heparin to achieve a therapeutic level of anticoagulation . what to do

Back 21

is principally the result of inadequate dosing.
Dosing nomograms help to standardize and improve therapy and facilitate achievement and maintenance of more rapid therapeutic levels of heparin

Front 22

what is measuring the heparin response,

Back 22

aPTT,

Front 23

Low-molecular-weight heparin (LMWH) is

Back 23

Low-molecular-weight heparin (LMWH) is a fragment of unfractionated heparin

Front 24

why LMWH has a greater relative ability to neutralize factor Xa that does thrombin

Back 24

Because LMWH lacks many of the larger monosaccharide chains (≥18) required for binding to thrombin, it has a greater relative ability to neutralize factor Xa than does thrombin

Front 25

why using LMWH doesnot requiring lab monitoring, except, perhaps, during pregnancy

Back 25

LMWH agents have a significantly reduced ability to bind to plasma proteins,
facilitating increased availability for binding to antithrombin, producing an anticoagulant effect,
and requiring no laboratory monitoring, except, perhaps, during pregnancy.
They are also more uniformly absorbed from subcutaneous depots and have a longer plasma half-life (range, 3 to 5 h).

Front 26

LMWH agents are excreted predominantly from,,,,

how to monitor

Back 26

LMWH agents are excreted predominantly from the kidney. Alteration of dosing is required in patients with renal failure for whom it is recommended that full-dose therapy be instituted only with the aid of anti-Xa–factor assay monitoring capability.

Front 27

Monitoring of LMWH may also be helpful in

Back 27

Monitoring may also be helpful in morbidly obese patients.

Front 28

indications for LMWH

Back 28

VTE prophylaxis,
treatment and prophylaxis of ischemic complications in the setting of acute coronary syndromes and ST-elevation myocardial infarction.

Front 29

Fondaparinux

Back 29

indirect inhibitor of factor Xa
has no antithrombin effect ( lacks the longer saccharide chains necessary for thrombin binding.)
predictable antithrombotic effect,
equires no coagulation monitoring.
good absorption from subcutaneous depots,
reaches peak concentrations in 1 to 3 hours
effective half-life of approximately 17 hours,
allowing for once-daily dosing.

Front 30

fondaparinux and hepatin induced thrombocytiopenia

Back 30

Although fondaparinux may induce heparin/platelet factor-4 antibodies, these antibodies rarely cause heparin-induced thrombocytopenia

Front 31

fondaparinux not recommended in patients

Back 31

It is excreted entirely by the kidneys and is not recommended in patients with renal impairment (creatinine clearance <30 mL/min).

Front 32

Fondaparinux when to give

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prophylaxis of VTE in patients undergoing hip or knee replacement surgery or hip fracture surgery
and in other medical or surgical conditions.
It is also approved for the treatment of acute DVT or pulmonary embolism.

Front 33

Fondaparinux, when initiated 4 to 8 hours after surgery, has been found to be superior to...... preventing VTE after total hip replacement, total knee replacement, and hip fracture surgery

Back 33

Fondaparinux, when initiated 4 to 8 hours after surgery, has been found to be superior to LMWH in preventing VTE after total hip replacement, total knee replacement, and hip fracture surgery. It has also been reported to be non-inferior to dalteparin in preventing postoperative VTE in patients who undergo high-risk abdominal surgery.

Front 34

Warfarin is indicated for the

Back 34

prevention or treatment of VTE;
for prevention of systemic embolism in patients with prosthetic heart valves or atrial fibrillation;
for the primary prevention of acute myocardial infarction in high-risk men;
for the prevention of:
stroke,
recurrent infarction,
death in patients with acute myocardial infarction.

Front 35

Pre- and Postoperative Bridging Guidelines for Patients Receiving Warfarin

Back 35

Stop warfarin therapy ~5 days preoperatively
Resume warfarin therapy ~12-24 h postoperatively if hemostasis is secure
If INR >1.5 the day before procedure, can administer oral vitamin K, 1-2 mg
For patients with MHV, AF, or VTE at high risk of TE, bridging with full-dose SC LMWH or IV UFH is recommended
For patients with MHV, AF, or VTE at moderate risk of TE, bridging with full-dose SC LMWH, IV UFH, or low-dose SC LMWH is recommended
For patients with MHV, AF, or VTE at low risk of TE, bridging with low-dose SC LMWH or no bridging is recommended
When possible, outpatient SC LMWH over inpatient IV UFH is recommended from a cost-saving perspective
Administer last dose of full-dose SC LMWH 24 h preoperatively at half the calculated dose
If receiving IV UFH, stop infusion at ~4 h preoperatively Resume full-dose SC LMWH for minor procedures ~24 h postoperatively if hemostasis is secured 1C
Resume full-dose SC LMWH/UFH for major procedures or high bleeding-risk procedures ~48–72 h postoperatively if hemostasis is secured, or low-dose SC LMWH/UFH when hemostasis is secure

Front 36

Direct Thrombin Inhibitors

Back 36

lepirudin, the recombinant form of the leech enzyme, hirudin;
bivalirudin, an engineered form of hirudin that alters its thrombin-binding capacity and half-life;
argatroban, a small molecule that binds irreversibly to the active site of thrombin

Front 37

Lepirudin and argatroban

Back 37

Lepirudin and argatroban are principally used as alternative anticoagulants for patients with HIT. Lepirudin is excreted in the urine and argatroban metabolized by the liver, attributes that often determine which of the two is to be used based on the patient’s comorbidities.

Front 38

Bivalirudin

Back 38

Bivalirudin is used in percutaneous coronary interventions as an alternative to unfractionated heparin. It is also approved for HIT in this setting.

Front 39

confirmatory diagnostic test in patients with suspected DVT. ??
the gold standard,???

Back 39

compression ultrasonography -confirmatory diagnostic.
In patients with DVT, compression ultrasonography will detect a noncompressible venous lumen, inside which echogenic material is visible. Contrast venography, the gold standard, is seldom used because of its invasiveness, cost, and associated morbidity.

Front 40

predicitive model for DVT probability

Back 40

each of the following characteristics earns 1 point: active cancer;
paralysis or recent plaster cast;
recent immobilization or major surgery;
tenderness along the deep veins;
swelling of the whole leg;
greater than a 3-cm difference in calf circumference compared with other leg;
pitting edema;
and collateral superficial veins.
Patients in whom an alternative diagnosis is likely earn -2 points.
A high probability for DVT exists in patients with a score of greater than 3;
a moderate probability exists in those with a score of 1 to 2; and low pretest probability exists in those with a score of 0 or less.

Front 41

who has the highest risk for DVT

Back 41

* Patients with idiopathic deep venous thrombosis and an elevated D-dimer have increased recurrence risk compared with patients in whom D-dimer levels are normal.

Front 42

tx in idiopathic deep venous thrombosis.

Back 42

an immediate-acting anticoagulant :
unfractionated heparin,
low-molecular-weight heparin,
or fondaparinux
for at least 5 days.

The appropriate treatment for a