Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Hematology > Thrombosis > Flashcards

Thrombosis Flashcards

1
Q

Thrombophilias that require LMWH in the antepartum and postpartum period.

A

Homozygous FVL, combine thrombophilias, APLA (plus ASA)

If + FmHx- Prothrombin 20210A, Antithrombin III

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

APLA clinical and lab criteria

A

Clinical:
Arterial or venous thrombosis or biopsy confirmed microthrombi in any organ
3 or more early pregnancy loss (<10 weeks)
1 or more pregnancy loss at >10 weeks or premature labour at <34 weeks related to preterm preeclampsia

Lab: (two positive measurements 12 weeks apart)
Positive Lupus Anticoagulant (must not be done on heparin, LMWH, DOACs or warfarin)
Anti B2 glycoprotein IgG or IgM >40 units
Anti-cardiolipin IgG or IgM >40 units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

5 causes of acquired Protein S and C deficiency

A

Protein C

  1. Warfarin
  2. Liver disease
  3. Vitamin K deficiency
  4. Acute thrombosis
  5. Protein losing enteropathy (IBD, nephrotic syndrome)

Protein S
*same as above + pregnancy/HRT/OCP and acute inflammatory states

Others: neonate, DIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

5 causes of acquired antithrombin deficiency

A
  1. Heparin
  2. L-asparginase
  3. Liver disease
  4. DIC & sepsis
  5. Acute thrombosis
  6. Protein losing enteropathy (nephrotic syndrome)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

3 in vivo inhibitors of fibrinolysis

A
  1. Thrombin activatable fibrinolysis inhibitor (TAFI)—>inhibits both FDPs and plasminogen
  2. Plasminogen activator inhibitor (PAI-1 and PAI-2)–> inhibit t-PA
  3. Alpha 2-Antiplasmin—>inhibits plasmin

Def of these agents leads to bleeding!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Superficial Vein Thrombosis, when to treat

A

<3cm from saphenofemoral junction–>Treat with full dose x 3months
>3cm from SFJ and >5cm–> Tx with proph AC
>3cm from SFJ and <5cm–> NSAIDs and observe with serial US

*consider treatment in pregnancy and symptomatic clots

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Name 4 ways in which cirrhosis leads to a prothrombotic state

A 
decreased Protein C 
decreased Protein S
Increased vWF
increased FVIII (endothelial)
Decreased portal +/- hepatic circulation leading to stasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name the 4 components of the prothrombinase complex

A

Xa
Va
Calcium
Phospholipid

Intrinsic Tenase: VIIIa, IXa, PL, Ca
Extrinsic Tenase: VIIa, TF, PL, Ca

The prothrombinase complex catalyzes the conversion of prothrombin (Factor II), an inactive zymogen, to thrombin (Factor IIa), an active serine protease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Risk of thrombosis with 1st gen, 2nd gen, 3rd gen, patch, oral HRT, progestin only?

*not sure if these are correct.

A

as per WHI/HER study, Oral HRT = 2 x increased risk
First and second generation risk of VTE = 3x increased risk
Third generation: 4x increased risk Higher than 2nd gen.
Patch (estrogen containing): 5x risk
Patch (progestin only): no risk
Progestin only: no risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What single test must be done routinely to monitor all of these NOACs?

What 2 tests are most sensitive for “determining the effect of anticoagulation” in patients treated with dabigatran?

What 1 test is most sensitive for “determining the effect of anticoagulation” in patients treated with rivaroxaban or apixaban?

What feature of dabigatran accounts for its ability to be dialyzed and what percentage of this feature is present in dabigatran compared to rivaroxaban and apixaban?

A
  1. What single test must be done routinely to monitor all of these NOACs?
    SCr
  2. What 2 tests are most sensitive for “determining the effect of anticoagulation” in patients treated with dabigatran?
    Ecarin clotting time. thrombin time.
  3. What 1 test is most sensitive for “determining the effect of anticoagulation” in patients treated with rivaroxaban or apixaban?
    Anti-Xa
  4. What feature of dabigatran accounts for its ability to be dialyzed and what percentage of this feature is present in dabigatran compared to rivaroxaban and apixaban?

Apixaban and Rivaroxaban are heavily protein bound, which limits the degree to which they can be removed via IHD

Dabigatran is 80% Renally cleared (30% protein bound)
Rivaroxaban is 65% renally cleared (90% protein bound)
Apixaban is 25% renally cleared (85% protein bound)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

In APLA what is the antibody that leads to the highest risk of obstetric and VTE complications

A

Lupus anticoagulant > anticardiolipin&raquo_space;> anti-beta2glycoprotein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

4 specific situations where you would transfuse antithrombin for a patient with congenital antithrombin deficiency

A

Pregnancy (with previous hx of VTE or new onset)
Surgery (cardiopulmonary surgery need of heparin)
VTE (if LMWH or if prophylactic is contraindicated)
Patient receiving asparginase
Post op for DVT proph

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Name 2 causes with different mechanisms for (acquired) low protein S

A 
Chronic Liver disease
Vitamin K deficiency
VKAs
Acute Thrombosis 
Pregnancy
Nephrotic Syndrome: reduced PS due to loss of free PS in the urine and an elevation in plasma C4b-binding protein concentration

Congenital (Neonatal Purpura Fulminans): AD inheritance, homozygous or double hetero

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Regarding reversal agents for NOACS (direct thrombin and direct anti-Xa:
Type of molecule
Mechanism of action

A

Idaracizumab - a monoclonal antibody fragment, binds dabigatran with an affinity that is 350x as high as that observed with thrombin → idarucizumab binds free and thrombin-bound dabigatran and neutralizes its activity

Andexanet - recombinant, modified human factor Xa decoy protein that binds factor Xa inhibitors but does not have intrinsic catalytic activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Complications of APLA in pregnancy

A
  1. Pre-eclampsia
  2. Arterial/venous thrombosis
  3. Intrauterine growth restriction
  4. Placental insufficiency
  5. Pre-term delivery with prematurity complications.

*ACL alone does not have increased thrombosis risk but DOES have risk of pregnancy complications.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Name three common target antigens for autoantibodies in patients with thrombosis and APS

A

IgG or IgM Anti-cardiolipin antibody
IgG or IgM anti-beta2 glycoprotein I abs
phosphatidylserine, plasmin, thrombin or prothrombin.
annexin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

In which patients would you not consider dose reduction of Apix/Riva according to Amplify-Extend and EINSTEIN, respectively?

A
  1. Obesity (wt>120mg)
  2. Needing thrombolytic with initial clot
  3. pHTN from PE
  4. Post thrombotic syndrome
  5. Active malignancies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Diagnostic criteria of CAPS?

A
  1. Evidence of involvement of three or more organs, systems, and/or tissues
  2. Development of manifestations simultaneously or in less than a week
  3. Confirmation by histopathology of small vessel occlusion in at least one organ or tissue
  4. Laboratory confirmation of the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and/or anti-beta2-glycoprotein I antibodies).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

3 procedures which do not require holding Warfarin

A
  1. Cataract
  2. Dental procedures (can hold x 2-3 days if preference)
  3. Derm procedures

(Can also stay on ASA, if on DAPT hold tica or prasugrel 5-7 days before)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

3 procedures in which require holding Warfarin

A

(i) prostate or kidney biopsy
(ii) large colonic polypectomies
(iii) cardiac pacemaker or defibrillator implantation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Homozygous or double hetero protein C deficiency, how does it present in children and what is the treatment?

A
  1. Neonatal purpura fulminans, protein C level usually undetectable
  2. Treat with FFP and LMWH and then transition to Warfarin indefinitely
  3. Protein C concentrates are approved for use in patients who have confirmed severe protein C deficiency. Generally, protein C should be administered for 6 to 8 weeks, until all lesions have healed and a therapeutic INR has been achieved. Liver transplant is curative.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What were the results of the TRIPP trial for Dalteparin in pregnant woman with history of placenta-mediated complications and thrombophilias?

A

Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Consequences of Warfarin in pregnancy

A
  1. Nasal hypoplasia
  2. Limb hypoplasia
  3. Stippled epiphyes (pattern of focal bone calcification.)
  4. Can increase bleeding in infant (consider switch to LMWH at 36 weeks)
  5. Dorsal midline dysplasia
  6. Optic atrophy

If needed for mechanical valve, give after 12 weeks. If very high risk, old mitral valve, can add ASA

Avoid at 6-12 weeks!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

HIT in pregnancy, what are the preferred treatments

A

1st line as per ASH.

  1. Danaparoid
  2. Fondaparinox
  3. Argatroban

Neither cross placenta

*HIT is rare in pregnancy!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Risk (in folds higher) of VTE in the following states:

  1. OCP
  2. Pregnancy
  3. Post partum
A

OCP- 2- to 3-fold greater (usually in first 3 months)
Pregnancy- 5- to 10- fold
Post-partum- 5- to 35-fold

26
Q

Estrogen increases which pro-coagulants and decreases which natural anti-coagulants?

A

Increases: Factor VIII,VWF, and fibrinogen
Decreases: fibrinolytic activity, protein S.

*primary cause is acquired protein C resistance!

27
Q

TPO evidence in chronic liver disease and pre-procedure.

A
  • Avatrombopag (Doptelet) is a new oral TPO receptor agonist approved for adults with chronic liver disease who require a rise in platelet count in order to undergo a procedure.
  • Eltrombopeg NOT approved as trial showed increased risk of PVT and hepatic decompensation.
28
Q

What are non-heparin alternatives that can be used in HIT and their MOA?

A
  1. Fondaparinux (weight based dosing; no monitoring required)- Synthetic pentasaccharide binds antithrombin III as a selective Xa inhibitor (not thrombin inhibition)
  2. Argatroban (infusion; rate based on PTT)- DTI
  3. Bivalirudin (infusion; initial rate to be adjust based on renal function; rate based on PTT)- DTI
  4. Danaparinoid (bolus with infusion; initial rate based on renal function; rate based on anti-Xa levels)- Xa and thrombin inhibitor
  5. DOACS
  6. Warfarin- CANNOT use until plts normalized
29
Q

Best non-heparin alternatives for AC in HIT in pt with renal dysfunction? Hepatic dysfunction?

A
  1. Argatroban

2. Fonda, Danaparoid, Bivalirudin

30
Q

What is the benefit of catheter directed thrombosis for proximal DVT? What was the effect of PTS development at 2 years?

A
  1. faster resolution of symptoms and improved canalization rates
  2. No change to PTS at 2 years
31
Q

What is May Thurner syndrome?

A

May-Thurner syndrome is the term used for the chronic compression of the left common iliac vein between the overlying right common iliac artery and the fifth lumbar vertebral body posteriorly.

in the patient with left-leg femoral or iliac DVT who successfully has received thrombolytics, correction of the stenosis using balloon angioplasty and stenting can be considered.

32
Q

3 mechanisms by which PTS develops?

A
  1. incompetent venous valves damaged by the thrombus
  2. associated inflammatory mediators
  3. impairment of venous return due to residual venous obstruction from incompletely cleared thrombus

30% develop mild-moderate, 5% develop severe.
CTEPH develops in 1% of PE pts within 6 months
at PE.

33
Q

Options for treatment of CTEPH?

A

chronic thromboembolic pulmonary hypertension (CTEPH)

Tx:

  1. pulmonary endarterectomy
  2. bosentan (an endothelin receptor antagonist)
34
Q

What are 3 superficial veins of the upper extremities? What 3 imaging modalities to assess for DVT in the UE?

A
  1. antecubital, cephalic, and basilic veins.

2. Doppler US, contrast venography (gold standard), and CT or MR venography

35
Q

Explain the role of activated protein C in the coagulation systems and why mutations in APC lead to FVL.

A

APC is a potent inhibitor of the coagulation system, cleaving the activated forms of factors V and VIII (FVa and FVIIIa). Protein S is a cofactor to this reaction.

FVL=point mutation (G1691A) in the factor V gene leads to abolishing a cleavage site for APC and makes factor Va less susceptible to inactivation.

36
Q

Heterzygous FVL mutation confers ___ fold increased risk of 1st VTE
Homozygous FVL mutation confers ___ fold increased risk of 1st VTE

A

Heterzygous FVL= 3-5 fold increased risk of 1st VTE

Homozygous FVL= 18 fold increased risk of 1st VTE

37
Q

What are the two types of protein C deficiency? Anti thrombin def?

A

Type I= quantitative deficiency with low functional protein C (activity) and immunologic (antigen) level
Type II=qualitative deficiency with low activity but normal antigen level.

For dx need to do Protein C activity (functional assay) or may miss type 2!

Same for antithrombin (Type 1 quant, Type 2 qual)

38
Q

What are the three types of protein S deficiency?

A

Type I= quantitative def, both free and total protein S antigen levels are decreased
Type II=qualitative defect due to a dysfunctional protein, in which protein S activity is low, but free and total antigen levels are normal
Type III= a quantitative deficiency, in which free protein S antigen level is low and the total antigen level is normal.

Need Protein S level and activity to make accurate diagnosis!

39
Q

What gives falsely low protein S levels?

A
  1. High factor VIII levels
  2. The presence of the FVL mutation
  3. The presence of a lupus anticoagulant
40
Q

What is the difference between Homocystinuria and hyperhomocysteinemia in terms of clinical VTE risk?

A

Homocystinuria- rare AR disorder, often present with VTE or ATE before the age of 30, also have dislocations of the lens.

hyperhomocysteinemia- may be due to def of vit B6, B12, or folate; renal impairment or polymorphisms in the genes (MTHFR) involved in the synthesis of the enzymes of the homocysteine metabolism.

Not a risk factor for VTE and decreasing level does not change thrombotic risk!

41
Q

What is the mechanism of action of Heparins? What are the differences between LMWH and UFH?

A

Heparins bind to and enhances the action of AT, which inactivates thrombin and factor Xa.

LMWHs inactivate mostly factor Xa, whereas UFH acts against thrombin and factor Xa.

(Fondaparinux is a synthetic pentasaccharide that binds to AT, leading to specific inactivation of factor Xa)

42
Q

4 reasons for Anti-Xa monitoring for a pt on LMWH

A
  1. Renal dysfunction
  2. Morbid obesity
  3. Children and neonates (poor predictability of wt based dosing compared to adults)
  4. Could be considered with breakthrough clot or bleedings to determine is supra or sub dosing.
43
Q

3 Causes of heparin resistance

A
  1. AT deficiency
  2. increased heparin clearance
  3. significantly low baseline aPTT (eg, due to elevations of factor VIII and fibrinogen)
  4. increased nonspecific heparin-binding proteins.
44
Q

Half life of Vit K dependent clotting factors

A 
FVII- 4-6 hrs
Protein C-8 hrs 
Factor IX- 24 hrs
Protein S- 30hrs
Factor X- 36 hrs
Factor II- 50 hrs
45
Q

What are the 6 components of the sPESI and what does a high score suggest?

A
  1. Age >80
  2. Hx of cancer
  3. Chronic cardiopulmonary dz
  4. Pulse >110
  5. BP <100
  6. Ao2 <90

if >/= to 1 point- 30 day mortality is 10%

Original PESI adds male sex, chronic HF and pulmonary dz (separated), RR >30, temp<36 and altered LOC

46
Q

Drug and dose of AC in Calisto trial

A

Fondaparinux 2.5mg SC daily x 45 days vs. placebo for SVT
Primary outcome was composite of (DVT, PE, death, extension to saphofemoral junction, recurrence of SVT)
0.9% vs. 5.9% (p<0.001)

High risk pts for VTE (eg, involvement of the great saphenous vein within 3 cm of the saphenofemoral junction, recent surgery, prior phlebitis or DVT, cancer) were excluded.

47
Q

Young woman with tumor and plt aggregates on peripheral blood film. What is this finding and what does it predispose to?

A

High aberrant expression of podoplanin (transmembrane sialoglycoprotein) in glioma patients–>activates platelets.

Leads to high risk of eventual development of VTE.

48
Q

In a pregnant patient with Ovarian hyperstimulation syndrome (OHSS) from IVF, how long do you extend prophylaxis LMWH in the post-partum period?

A

12 weeks AFTER clinical recovery of OHSS (weight stable, GI symptoms resolved).

49
Q

Which of the coagulation factors are decreased following acute clot?

A
  1. Protein C
  2. Protein S
  3. Anti-thrombin III

(FVL and prothrombin 20210A can be tested at any time).

50
Q

Which DOAC has a slightly lower intracranial bleed risk compared to Warfarin

A

Dabigatran

51
Q

Describe why patients with triple positive antiphospholipid antibody syndrome and previous venous thromboembolism should not receive direct oral anticoagulants for secondary thrombosis prevention. Please list the clinical trial in which this was identified.

A

Traps trail, compared rivaroxaban 20mg or warfarin INR2.5. In triple positive APLAS more thrombotic (arterial) in rivaroxaban arm.

52
Q

Reduction of Apixiban in Afib requires 2 of what 3 factors?

A
  1. Age>/=80
  2. Cr >/= 133
  3. Weight <60kg
53
Q

Pt with extensive DVT, whole leg dusky/cyanotic and in extreme pain. What is the term for this?

A

Phlegmasia cerulea dolens

54
Q

4 scenarios that you must use Warfarin over DOAC?

A
  1. Mechanical cardiac valve
  2. Kidney disease with CrCl low or dialysis
  3. Triple positive APLAS
  4. Therapeutic anticoagulation when breast feeding
  5. HIT
55
Q

3 naturally occurring promoters of fibrinolysis, ie. fibrin breakdown?

A
  1. Tissue plasminogen activator (t-PA)
  2. Urokinase
  3. Streptokinase
56
Q

What are common sites of bleeding in the following rare factor deficiencies:

  1. FVII
  2. FX
  3. FXIII
  4. FXI
  5. II
A
  1. FVII- intracranial (unlikely with factor VII activity levels >10%). muscle, mucosal, menstrual.
  2. FX- intracranial, invasive procedures, umbilical cord, joint and muscle bleeding.
  3. FXIII- intracranial, umbilical stump bleeding (can also be associated with miscarriages, and poor wound healing).
    - Can develop after cardiopulmonary bypass and with IBD.
  4. FXI- surgery or injury related, GI or GU
  5. II- excessive bleeding after invasive procedures, and umbilical cord, joint, muscle, and mucosal bleeding
  6. FV- excessive bleeding after invasive procedures and mucosal tract bleeding (can occur along with FVIII def).

Recombinant products for FXI and FXIII but not widely available.

57
Q

VTE dosing for the following:

  1. Apixiban
  2. Rivaroxaban
  3. Dabigatran
  4. Edoxaban
  5. Dalteparin
  6. Enoxaparin
  7. Tinzaparin
A
  1. Apixiban 10mg PO BID x7 days, then 5mg PO BID
  2. Rivaroxaban 15mg PO BID x 21 days, then 20mg PO daily
  3. Dabigatran–> 5-10 days with parental overlap then 150mg PO BID
  4. Edoxaban–> 5-10 days with parental overlap then 60mg PO daily (or 30mg PO daily if wt <60kg)
  5. Dalteparin 200 units/kg daily or 100units/kg BID
  6. Enoxaprin 1.5mg/kg daily or 1mg/kg BID
  7. Tinzaparin 175units/kg daily.
58
Q

Prophylactic dosing of VTE dosing for the following:

  1. UFH
  2. Dalteparin
  3. Enox
  4. Tinzaparin
  5. Fondaparinux
  6. Apixiban (AVERT)
  7. Rivaroxaban (Cassini)
A
  1. UFH 5000 units q12 hours
  2. Dalteparin 5000 units daily
  3. Enox 40 mg daily
  4. Tinzaparin 4500 daily
  5. Fondaparinux 2.5 mg once daily
  6. Apixiban 2.5mg BID
  7. Rivaroxaban 10mg daily
59
Q

Factors in the khorana score, what is the cutoff for suggesting anticoagulation for cancer patients in the outpt setting?

A

FAT SITE COUNTS 3

  1. Site of primary tumor
    - Very high risk (gastric, pancreas) (2 pts)
    - High risk (lung, lymphoma, gynecologic, bladder, testicular) (1 pts)
    - All other sites (0)
  2. Pre-chemotherapy platelet count ≥350 (1 pt)
  3. Hemoglobin level <100 or use of ESAs (1 pt)
  4. Pre-chemotherapy WBC >11 (1 pt)
  5. BMI ≥35 kg/m2 (1 pt)

Cut offs:
low=0 pts
Int= 1-2 pts (only consider if pt preference to avoid VTE and understanding of bleeding risk)
High= >3 (consider proph dose AC)

  • May also consider if prior VTE or severe immobility
  • Trials AVERT and CASSINI
60
Q

Main findings of Cassini and AVERT trials in ambulatory cancer patients?

A

Cassini

  • Rivaroxaban 10mg PO BId vs placebo, Khorana >/= 2
  • Did pre-randomization dopplers in both groups
  • ARR 2% of VTE, increased major bleeding but not statistically significant
  • intracranial malignancy not included

AVERT

  • Apixiban 2.5mg PO BID vs placebo, Khorana >/=2
  • Included intracranial malignancy
  • No pre-randomization dopplers
  • 6% ARR for VTE
  • Major bleeding 3.5% vs. 1.8% in Apix group but major bleeding during on-treatment period only was not significant.
61
Q

Name 4 superficial veins in the lower extremities?

A
  1. Telangiectasias or reticular veins
  2. Great saphenous vein above the knee
  3. Great saphenous vein below the knee
  4. Small saphenous vein
  5. Nonsaphenous veins

Distal DVT common veins: posterior tibial and peroneal veins while anterior tibial and muscular vein dDVTs are uncommon.

62
Q

3 drugs that interact with anti-XA inhibitor

A
  1. Rifampin
  2. Dilantin
  3. Carbamazepine

Hematology (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions