Treatment of Venous Thromboembolism:

Thrombophilia Testing
An Educational Slide Set
American Society of Hematology Guidelines for the Management of
Venous Thromboembolism: Thrombophilia Testing

Slide set authors:

Taylor Dear, MD (University of Toronto)
Nicole Relke, MD (University of Toronto)
Zachary Liederman, MD MScCH (University of Toronto)
Saskia Middeldorp, MD, PhD (Radboud University Medical Center)
Clinical Guidelines
American Society of Hematology 2023 Guidelines for
Management of Venous Thromboembolism:
Thrombophilia Testing

Middeldorp S, Nieuwlaat R, Baumann Kreuziger L, Coppens M,

Houghton D, James A, Lang E, Moll S, Myers T, Bhatt M, Chai
Adisaksopha C, Colunga Lozano LE, Karam SG, Zhang Y,
Wiercioch W, Schünemann HJ, Iorio A
ASH Clinical Practice Guidelines on VTE
1. Prevention of VTE in Surgical Hospitalized Patients
2. Prevention of VTE in Medical Hospitalized Patients
3. Diagnosis of VTE
4. Optimal Management of Anticoagulant Therapy
5. Heparin-Induced Thrombocytopenia (HIT)
6. VTE in the Context of Pregnancy
7. Thrombophilia Testing
8. Treatment of Pediatric VTE
9. Treatment of Acute VTE (DVT and PE)
10. Prevention and Treatment of VTE in Patients with Cancer
11. Anticoagulation in Patients with COVID-19
12. Adaptation of ASH Management of VTE Guidelines for Latin America
How were these ASH guidelines developed?
PANEL FORMATION CLINICAL QUESTIONS EVIDENCE SYNTHESIS MAKING
Each guideline panel was 20-30 clinically-relevant Evidence summary RECOMMENDATIONS
formed following these key questions generated in generated for each PICO Recommendations
criteria: PICO format (population, question via systematic
made by guideline
• Balance of expertise intervention, comparison, review of health effects
(including disciplines outcome) plus: panel members based
beyond hematology, • Resource use on evidence for all
and patients) • Feasibility factors.
• Close attention to • Acceptability
minimization and • Equity
Example: PICO question
management of COI “Should thrombolytic therapy in
• Patient values and
addition to anticoagulation vs. preferences
anticoagulation alone be used for
patients with extensive proximal
DVT??”

ASH guidelines are reviewed annually by expert work groups convened by ASH. Resources, such as this
slide set, derived from guidelines that require updating are removed from the ASH website.
How patients and clinicians should use these recommendations

STRONG Recommendation CONDITIONAL Recommendation

(“The panel recommends…”) (“The panel suggests…”)

Most individuals would want the A majority would want the intervention,
For patients
intervention. but many would not.

Different choices will be appropriate

For Most individuals should receive for different patients, depending on
clinicians the intervention. their values and preferences. Use
shared decision making.
Grading the quality of evidence
Introduction
Thrombophilia: acquired or hereditary conditions with higher-than-normal risk of VTE
Thrombophilia testing has several potential advantages and disadvantages:
Advantages Disadvantages
Improved risk stratification Risk of false negatives (missed
of VTE diagnosis) and false positives
(overdiagnosis)
Guides treatment and prevention Potential for physical,
of VTE psychological, or financial harm to
patients

Guideline purpose: Provide evidence-based recommendations about whether thrombophilia testing and
tailoring management based on results, improves patient-important outcomes.
Objectives

By the end of the session, you should be able to:

1. Review the prevalence and risks associated with hereditary thrombophilia

2. Describe when thrombophilia testing may be indicated in patients with
symptomatic VTE
3. Describe recommendations for thrombophilia testing in asymptomatic
patients with a family history of VTE/thrombophilia
For each clinical question, the panel compared two scenarios:
Thrombophilia Testing Intervention in
only the individuals found to have the
thrombophilia
No thrombophilia Testing
Usual care in all individuals

Depending on the specific question, for

patients positive for thrombophilia,
interventions include:
• Indefinite Anticoagulation
• Thromboprophylaxis
• Avoidance of Thrombotic Risk Factor
Treatment (anticoagulation) effect

For example, in a patient with a history of a provoked VTE, where stopping anticoagulation is usual care:

Indefinite ↑Bleeding
Thrombophilia
Anticoagulation ↓Thrombosis

Thrombophilia Testing
No Thrombophilia Stop Anticoagulation

No Thrombophilia Stop Anticoagulation

Status Unknown
Testing in All

In providing a recommendation, the panel considered:

• Risk of bleeding vs. recurrent thrombosis
• Cost & burden of thrombophilia testing/anticoagulant treatment
• Patient preferences
Thrombophilia testing in patients with VTE
Prevalence, RR for VTE Treatment effect for Treatment effect for
Median % Recurrence - Positive VTE recurrence, RR major bleeding, RR
(Min-Max) vs Negative (95% CI) (95% CI) (95% CI)

Any Thrombophilia 38.0 (21.6-59.5) 1.65 (1.28-2.47)

Low Risk
FVL Heterozygous 17.5 (4.1-34.8) 1.36 (1.19-1.57)

Prothrombin gene mutation 6.1 (1.4-16.3) 1.34 (1.05-1.71)

High Risk 0.15 2.17
(0.10-0.23) (1.40-3.35)
FVL Homozygous 1.5 (0.3-3.1) 2.10 (1.09-4.06)

Antithrombin (AT) Deficiency* 2.2 (0.2-8.7) 2.07 (1.50-2.87)

Protein C (PC) Deficiency* 2.5 (0.7-8.6) 2.13 (1.26-3.59)

Protein S (PS) Deficiency * 2.3 (0.7-7.3) 1.30 (0.87-1.94)

*Results influenced by hormone use, timing of testing and anticoagulation

Case 1: Unprovoked VTE
52 year old male

Past Medical History: None

Diagnosis: Unprovoked symptomatic right leg DVT

Treatment: He has been treated with anticoagulation for 3 months without any
bleeding concerns
Usual Care
Indefinite antithrombotic therapy is suggested in most individuals with unprovoked VTE
(Treatment of VTE ASH guideline)
Thrombophilia testing strategy would mean that patients without thrombophilia would stop anticoagulant
therapy (potential for more thrombosis and less bleeding)

What management strategy do you suggest?

a. No thrombophilia testing and indefinite anticoagulation

b. Thrombophilia testing and stop anticoagulation in patients without thrombophilia
Recommendation 1
In patients with unprovoked VTE who have completed primary short term treatment, the ASH guideline
panel suggests not to perform thrombophilia testing to guide the duration of anticoagulant treatment
(conditional recommendation, low certainty)

Impact of thrombophilia testing strategy per 1000 patients

Outcomes
(620 fewer patients treated with indefinite anticoagulation)

Recurrent VTE 42 more VTE recurrences (ranging from 17 to 67)

Major Bleeding - Low Risk

(0.5% per year) 4 fewer major bleeds (ranging from 1 to 9)

Major Bleeding – High Risk

(1.5% per year) 11 fewer major bleeds (ranging from 2 to 28)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Case 2: Provoked VTE
35-year-old female

Past Medical History: Hypertension

Past Surgical History: Appendectomy

Diagnosis: Pulmonary embolism on post-operative day 21 following appendectomy

Treatment: She is started on anticoagulation and referred for outpatient assessment

Usual Care
Individuals with VTE provoked by surgery discontinue anticoagulant therapy after primary treatment
(Treatment of VTE ASH guideline)

Thrombophilia testing strategy would mean that patients with thrombophilia would receive indefinite
anticoagulant therapy (potential for less thrombosis and more bleeding)

What management strategy do you suggest?

a. No thrombophilia testing, treat for 3 months and stop anticoagulation

b. Thrombophilia testing and indefinite anticoagulation only in patients with thrombophilia
Recommendation 2
In patients with VTE provoked by surgery who have completed primary short-term treatment,
the ASH guideline panel suggests not to perform thrombophilia testing to determine the duration
of anticoagulation treatment (conditional recommendation, very low certainty of evidence)
Impact of thrombophilia testing strategy per 1000 patients
Outcomes
(380 more patients treated with indefinite anticoagulation)

Recurrent VTE 4 fewer VTE recurrences (ranging from 2 to 7)

Major Bleeding - Low

2 more major bleeds (ranging from 0 to 7)
Risk (0.5% per year)

Major Bleeding - High

7 more major bleeds (ranging from 1 to 21)
Risk (1.5% per year)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Case 3: Pregnancy
24-year-old female, G1P0, 35+3 weeks gestation

Past Medical History: None

Diagnosis: Left leg DVT after presenting with a 2-day history of increasing left leg
swelling and pain

Treatment: She is started on anticoagulation and referred for outpatient assessment

Usual Care
Individuals with VTE provoked by pregnancy will discontinue anticoagulant therapy after primary
treatment (Treatment of VTE ASH guideline)

Thrombophilia testing strategy would mean that patients with thrombophilia would receive
indefinite anticoagulant therapy (potential for less thrombosis and more bleeding)

What management plan do you suggest?

a. No thrombophilia testing, treat for 3 months and stop anticoagulation

b. Thrombophilia testing and indefinite anticoagulation only in patients with thrombophilia
Case 4: Non-Surgical Major Transient Risk Factor
64-year-old male

Past Medical History: None

Medications: Naproxen PRN

Diagnosis: Left leg DVT diagnosed on day 3 of admission for pneumonia. While in
hospital he is relatively immobile, only getting up to use the washroom

Treatment: He is started on anticoagulation and referred for outpatient assessment

Usual Care

Individuals with VTE provoked by non-surgical major transient risk factors will discontinue anticoagulant
therapy after primary treatment (Treatment of VTE ASH guideline)

Thrombophilia testing strategy would mean that patients with thrombophilia would receive indefinite
anticoagulant treatment (potential for less thrombosis and more bleeding)

What management plan do you suggest?

a. No thrombophilia testing, treat for 3 months and stop anticoagulation

b. Thrombophilia testing and indefinite anticoagulation only in patients with thrombophilia
Recommendations 3-5

In patients with VTE provoked by a non-surgical major transient risk factor, combined oral
contraceptives, pregnancy or postpartum who have completed primary short-term treatment, the panel
suggests testing for thrombophilia to guide anticoagulant treatment duration (conditional
recommendation, very low certainty)

Impact of thrombophilia testing strategy per 1000 patients

Outcomes
(380 more patients treated with indefinite anticoagulation)

Recurrent VTE 21 fewer VTE recurrences (ranging from 10 to 35)

Major Bleeding - Low

2 more major bleeds (ranging from 0 to 7)
Risk (0.5% per year)

Major Bleeding - High

7 more major bleeds (ranging from 1 to 21)
Risk (1.5% per year)

Quality of Evidence (GRADE): Low or Very Low Moderate High

American Society of Hematology 2020 Guidelines
(Treatment of VTE)
Transient Risk Factors Chronic (Persistent) Risk Factors
(resolve after provoked VTE) (persistent after VTE occurs)
Major Risk Factor • Active cancer (ongoing chemo;
• Surgery, gen anesthesia > 30 min recurrent or progressive disease)
• Confined to hospital bed ≥ 3 days with • Inflammatory bowel disease
acute illness • Autoimmune disorder (e.g.,
• Cesarean section antiphospholipid syndrome,
rheumatoid arthritis)
• Chronic infection
Minor Risk Factor
• Estrogen therapy (OCP, HRT) • Chronic immobility (e.g., spinal cord
injury)
• Pregnancy, puerperium
• Confined to bed out of hospital ≥ 3 days
with acute illness
• Leg injury, reduced mobility ≥ 3 days

Ortel Blood Adv 2020

Case 5: Unusual site thrombosis

44-year-old male assessed in follow up

Past Medical History: Hypertension

Diagnosis: Unprovoked cerebral venous thrombosis diagnosed 2 years earlier

Treatment: In discussion with the patient, you have decided to continue with indefinite
anticoagulation
Guidelines are indecisive on duration of anticoagulation for unusual site VTE
Thrombophilia testing strategy impact is dependent on clinicians' usual care.
Primary short term treatment only planned – patients with thrombophilia would receive indefinite
anticoagulant treatment (potential for less thrombosis and more bleeding)
Indefinite anticoagulation planned – patients without thrombophilia would stop anticoagulant therapy
(potential for more thrombosis and less bleeding)

The patient is interested in thrombophilia testing.

What management plan do you suggest?
a. No thrombophilia testing and indefinite anticoagulation
b. Thrombophilia testing and stop anticoagulation if negative
Recommendations 7-8
In patients with Cerebral Venous Thrombosis who have completed primary short-term treatment, the panel suggests testing for
thrombophilia to guide anticoagulant treatment duration only if anticoagulation would be discontinued otherwise (conditional
recommendation, very low certainty)

Impact of thrombophilia testing strategy per 1000 patients

Additional factors may
Indefinite anticoagulant influence thrombophilia
Primary treatment only planned
therapy planned
Outcomes (436 more patients treated with testing/ treatment and
(564 fewer patients treated with
indefinite anticoagulation) were not included in
indefinite anticoagulation)
analysis
Recurrent VTE 18 fewer VTE recurrences (14 to 23) 14 more VTE recurrences (10 to 18)
• Provoked vs.
Major Bleeding - Low Risk 3 more major bleeds (1 to 5) 3 fewer major bleeds (1 to 7) unprovoked
• Additional
Major Bleeding - High Risk 8 more major bleeds (3 to 16) 10 fewer major bleeds (3 to 20) thrombophilia (e.g.
JAK 2 mutation)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Summary of Thrombophilia Testing Strategy for Patients with VTE

Treatment
Base Risk of VTE Intermediate Risk of
Risk for Recommended Strategy
Recurrence
Major for Thrombophilia Testing recurrent thrombosis:
(1st year)
Bleeding Testing can tip the balance
Unprovoked High (10%) Do Not Test (indefinite anticoagulation in all) towards indefinite
anticoagulation
Do Not Test (indefinite anticoagulation in all) (thrombophilia positive
Intermediate OR recurrent VTE risk > bleeding
Unusual Site
(2.7%-3.8%) Test (indefinite anticoagulant therapy in patients risk)
with thrombophilia)
0.5-1.5%
Provoked Test (indefinite anticoagulant therapy in patients High or Low Risk of recurrent
Intermediate (5%)
(non-surgical) with thrombophilia) thrombosis: Testing does not
cross treatment thresholds
Provoked Do Not Test (primary short-term anticoagulation (i.e. for unprovoked VTE,
Low (1%)
(surgical) in all) recurrent VTE risk > bleeding
risk regardless of
thrombophilia test results)
Introduction to thrombophilia testing in individuals with a
family history of VTE and/or thrombophilia
In families with VTE, the panel examined patient outcomes from testing asymptomatic individuals
(relatives) for thrombophilia

The panel considered two scenarios:

1. Known specific thrombophilia in affected family member (proband)
• Selective thrombophilia testing

2. Unknown thrombophilia status

• Panel thrombophilia testing

When outcomes were similar, the panel favored selective over panel testing
Thrombophilia testing in individuals with family history of VTE

Treatment effect for Treatment effect for Panel Testing: testing for
RR for 1st VTE - Positive vs
VTE occurrence, major bleeding, APLA and all hereditary
Negative (95% CI)
RR (95% CI) RR (95% CI)
thrombophilia types
Low Risk
Selective Thrombophilia
FVL Heterozygous 2.71 (2.06-3.56) Testing: testing for a
Prothrombin (PT) Mutation 2.35 (1.46-3.78) specific thrombophilia
type (i.e. family testing)
High Risk 0.54 2.09
(0.32-0.91) (1.33-3.27)
Antithrombin (AT) Deficiency 12.17 (5.45-27.17)

Protein C (PC) Deficiency 7.47 (2.81-19.81)

Protein S (PS) Deficiency 5.98 (2.45-14.57)
Case 6: Family history of VTE and minor provoking risk factor
22-year-old female is assessed as an outpatient following a severe high grade ankle
sprain being managed non-operatively. Non-weightbearing and immobilization are
recommended for the next 10 days

Past Medical History: None

Medications: None

Family History: Mother has a history of DVT. To her knowledge, her mother has not
been tested for thrombophilia
Usual Care
No thromboprophylaxis for medical outpatients with minor provoking risk factors for VTE (Prophylaxis for
Medical Patients ASH guideline)

Thrombophilia testing strategy would mean that individuals with thrombophilia would receive
thromboprophylaxis for a minor provoking factor (potential for less thrombosis and more bleeding)

What management plan do you suggest?

a. No thrombophilia testing and no thromboprophylaxis

b. Thrombophilia testing and start anticoagulant thromboprophylaxis if positive
Recommendation 13
In individuals with a minor risk factor who have a family history of VTE and unknown thrombophilia status,
suggest not to perform thrombophilia testing to guide thromboprophylaxis (conditional recommendation,
very low certainty)

Impact of thrombophilia testing strategy in first

degree relatives of patients with VTE per 1000 Recommendations
Outcomes assume no time delay
episodes (142 more patients receive
thromboprophylaxis) for testing

Recurrent VTE 2.16 fewer VTE (0.02 to 5.66)

Major Bleeding 0.62 more major bleeds (0.13 to 1.82)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Recommendations 11-12
In individuals with a minor provoking risk factor who have a family history of VTE and known thrombophilia, suggest thrombophilia testing to guide
thromboprophylaxis for high risk thrombophilia but not low risk thrombophilia (conditional recommendation, very low certainty)

Impact of selective thrombophilia strategy in first degree relatives of patients with VTE
Family History per 1000 episodes (500 more patients treated with thromboprophylaxis)
VTE Major Bleeding
Low Risk
FVL Heterozygous 5.04 fewer VTE (0.91 to 7.96)

Prothrombin mutation 4.84 fewer VTE (0.80 to 8.07)

High Risk 2.18 more bleeds

(0.66 to 4.54)
Antithrombin Deficiency 21.25 fewer VTE (3.80 to 32.79)

Protein C Deficiency 20.28 fewer VTE (3.32 to 32.37)

Protein S Deficiency 19.79 fewer VTE (3.20 to 31.82)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Case 7: Combined Oral Contraceptive (COC) pill or Hormone Replacement
Therapy (HRT) use
The same patient is re-referred 2 years later. She would like to start the combined oral
contraceptive pill for pregnancy prevention

Her past medical history is unchanged and she is not on any regular medications

Since the initial visit, her sister developed an unprovoked PE and was found to have
Protein C Deficiency
Thrombophilia testing strategy would mean that individuals with thrombophilia would avoid
COC and HRT (potential for less thrombosis)

She is looking to start combined oral contraceptive pill for prevention of pregnancy.

What management plan do you suggest?

a. No thrombophilia testing and start COC

b. Thrombophilia testing and suggest against COC if positive
Recommendations 19-20
In individuals with a family history of VTE and known thrombophilia, suggest selective thrombophilia testing to
guide COC or HRT for high risk thrombophilia only (conditional recommendation, very low certainty)
Impact of selective thrombophilia testing strategy on VTE episodes per 1000
women who are first degree relatives of patients with VTE / year (500 fewer
Family History using COC or HRT)*
COC HRT
Low Risk
FVL Heterozygous 4.57 fewer VTE (3.75 to 5.55) 1.36 fewer VTE (0.21 to 1.96)

Prothrombin mutation 4.38 fewer VTE (3.76 to 4.90) 2.20 fewer VTE (0.25 to 4.79)
High Risk
Antithrombin Deficiency 19.39 fewer VTE (15.30 to 23.90) 6.45 fewer VTE (0.77 to 13.49)

Protein C Deficiency 13.84 fewer VTE (11.34 to 15.45) 4.94 fewer VTE (0.60 to 10.12)

Protein S Deficiency 10.49 fewer (8.71 to 11.48) 3.92 fewer VTE (0.47 to 7.87)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Recommendations 15-18
In individuals from the general population suggest not to perform thrombophilia testing to guide the use of COC
(strong recommendation, low certainty) or HRT (conditional recommendation, low certainty)
In individuals with a family history of VTE and unknown thrombophilia, suggest not to perform thrombophilia
testing to guide the use of COC or HRT (conditional recommendation, very low certainty)

Impact of thrombophilia testing strategy The potential harms of

on VTE per 1000 women / year
(69-142 fewer using COC or HRT)* hormone avoidance fall
outside the guidelines
COC HRT scope but may include
unwanted pregnancies and
postmenopausal
0.26 fewer VTE 0.29 fewer VTE
General Population symptoms.
(0.09 to 0.65) (0.01 to 1.98)

Family History of VTE (1st 1.17 fewer VTE 0.94 fewer VTE
degree) and Unknown Thrombophilia (0.06 to 1.55) (0.01 to 5.16)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Case 8: Women who are planning pregnancy
26 year old female is planning to become pregnant, and was referred for a family history
of VTE and FVL. The patient has not undergone testing for thrombophilia, and she has no
history of VTE

Past Medical History: None

Medications: None

Family History: Sister has a history of DVT and is homozygous for FVL
Usual Care
No antepartum or postpartum thromboprophylaxis for women with no or 1 clinical risk factor
(Pregnancy ASH guideline)
Thrombophilia testing strategy would mean that patients with thrombophilia would receive antepartum
and/or postpartum thromboprophylaxis (potential for less thrombosis and more bleeding)
She is planning a pregnancy.

What management plan do you recommend?

a. Test for all inherited thrombophilias (FVL, PGM, Protein C / S, ATIII) and
start thromboprophylaxis if positive
b. No inherited thrombophilia testing and do not start thromboprophylaxis
c. Selective thrombophilia testing (FVL only) and start thromboprophylaxis if FVL homozygous
 Recommendation 21
In women with a family history of VTE and homozygous FVL, combination of FVL and PGM, or antithrombin
deficiency in the family, suggest testing for the known familial thrombophilia and antepartum thromboprophylaxis
in women with the same familial thrombophilia (conditional recommendation, very low certainty)

Impact of selective thrombophilia testing strategy per 1000 pregnancies

Family History In women with a family
(Antepartum thromboprophylaxis used in 250-500* more pregnancies)
history of VTE and known
Homozygous FVL 19.35 fewer VTE (12.16 to 24.14) protein C or S deficiency
1.05 fewer bleeds in the family, the panel
(1.52 fewer to 3.50 more) suggests either testing or
Combination of FVL and PGM 9.05 fewer VTE (4.63 to 12.33)
not testing to guide
Antithrombin deficiency 9.70 fewer VTE (5.90 to 11.97) antepartum prophylaxisO

2.09 fewer bleeds

Protein C deficiency 2.02 fewer VTE (0.82 to 2.66)
(3.04 fewer to 7.01 more)
Protein S deficiency 3.94 fewer VTE (1.34 to 5.32)

*250 more pregnancies for family history of homozygous FVL or combination of FVL and PGM; 500 more pregnancies for family
history of antithrombin deficiency, protein C deficiency or protein S deficiency
Quality of Evidence (GRADE): Low or Very Low Moderate High
 Recommendation 22
In women with a family history of VTE and a high risk thrombophilia (including combination of FVL and PGM),
suggest testing for the known familial thrombophilia and postpartum thromboprophylaxis in women with the same
familial thrombophilia (conditional recommendation, very low certainty)

Impact of thrombophilia strategy per 1000 pregnancies (Postpartum

Family History ASH guidelines on the
thromboprophylaxis used in 250-500* more pregnancies)
management of VTE in
Homozygous FVL 19.35 fewer VTE (12.16 to 24.14) pregnancy suggest against
1.06 fewer bleeds postpartum
(3.51 fewer to 10.07 more) thromboprophylaxis to
Combination of FVL and PGM 9.05 fewer VTE (4.63 to 12.33)
prevent a first VTE in
Antithrombin deficiency 9.70 fewer VTE (5.90 to 11.97) individuals with FVL
heterozygosity or PGM
0.53 fewer bleeds
Protein C deficiency 2.02 fewer VTE (0.82 to 2.66)
(1.76 fewer to 5.03 more)
Protein S deficiency 3.94 fewer VTE (1.34 to 5.32)

*250 more pregnancies for family history of homozygous FVL or combination of FVL and PGM; 500 more pregnancies for family
history of antithrombin deficiency, protein C deficiency or protein S deficiency
Quality of Evidence (GRADE): Low or Very Low Moderate High
Case 9: Patients with cancer and family history VTE

65 year old man from home with stage II head and neck cancer is seen in clinic before
starting systemic chemotherapy

Past Medical History: Hypertension

Medications: Ramipril

Family History: Brother has a history of pulmonary embolism

Usual Care
No thromboprophylaxis for ambulatory cancer patients receiving systemic therapy at low to intermediate
risk of thrombosis (Prevention and Treatment in Patients with Cancer ASH Guideline)

Thrombophilia testing strategy would mean that patients with thrombophilia would receive
thromboprophylaxis (potential for less thrombosis and more bleeding)

What management plan do you recommend before starting systemic chemotherapy?

a. No thrombophilia testing and do not start thromboprophylaxis

b. Testing for hereditary thrombophilia and thromboprophylaxis if positive
Recommendation 23
In ambulatory cancer patients receiving systemic therapy who have a family history of VTE and are at
low or intermediate risk for VTE, the panel suggests testing for hereditary thrombophilia and starting
thromboprophylaxis if positive (conditional, very low certainty)

Impact of thrombophilia testing strategy per 1000 patients ASH VTE Cancer guidelines
who are first degree relatives of patients with VTE/ 6 months
(142 more patients receive thromboprophylaxis) suggest using direct oral
anticoagulant
(DOAC) prophylaxis in all
VTE Major Bleeding
ambulatory cancer patients
receiving systemic therapy
6.85 fewer VTE 0.33 more bleeds
Low Risk for VTE with high VTE risk
(23.37 fewer to 0.16 more) (0.10 fewer to 2.02 more)

9.04 fewer VTE 0.74 more bleeds

Intermediate Risk for VTE
(30.85 fewer to 0.21 more) (0.22 fewer to 4.49 more)

Quality of Evidence (GRADE): Low or Very Low Moderate High

Other guideline recommendations that were not directly covered
in this session
Thrombophilia testing for:

• Unspecified VTE (Recommendation 6)

• Splanchnic vein thrombosis (Recommendations 9-10)
• Family history of thrombophilia but no family history of VTE to prevent VTE associated
with minor risk factors (Recommendation 14)
Future Priorities for Research
• Risk of recurrent VTE and its association with prognostic variables
• Optimal duration of anticoagulant therapy after acute cerebral venous
thrombosis or acute splanchnic venous thrombosis
• Large implementation studies comparing the impact (outcomes rates)
among management strategies involving thrombophilia testing
• Online calculator for specific thrombophilia defects incorporating
localized prevalence values
In Summary: Back to Our Objectives
1. Review the prevalence and risks associated with hereditary thrombophilia
2. Describe when thrombophilia testing may be indicated in patients with
symptomatic VTE
3. Describe recommendations for thrombophilia testing in asymptomatic patients
with a family history of VTE/thrombophilia