What is the data behind utilizing DOACs for HIT and HITT? Are there guidelines that now recommend DOACs for the treatment of HIT or HITT?

Comment by InpharmD Researcher

The 2018 American Society of Hematology (ASH) guidelines for heparin-induced thrombocytopenia (HIT) recommends apixaban, dabigatran, and rivaroxaban as reasonable options in clinically stable patients at an average risk of bleeding. Drug and patient-related factors should guide the choice of agent. Results from recent clinical trials report the successful use of these agents for the management of HIT and heparin-induced thrombocytopenia and thrombosis with a relatively low incidence of bleeding or thrombotic complications. As most studies had a retrospective design and small sample size, future studies are required to elucidate the optimal dosing regimens and the timing of initiation of each DOAC, with or without transition from a parenteral anticoagulant.
  

Pubmed: ​​ direct acting oral anticoagulants AND heparin induced thrombocytopenia, filter clinical trial- 18 results- none added Apixaban AND heparin induced thrombocytopenia, filter last 5 years- 32 results rivaroxaban AND heparin induced thrombocytopenia, filter last 5 years- 34 results dabigatran AND heparin induced thrombocytopenia, filter last 5 years- 15 results

Background

In patients with acute heparin-induced thrombocytopenia (HIT) complicated by thrombosis (HITT) or acute HIT without thrombosis (isolated HIT), 2018 American Society of Hematology (ASH) guidelines recommend discontinuation of heparin and initiation of a non-heparin anticoagulant. The choice of agent may depend on drug or patient-related factors. Apixaban, dabigatran, or rivaroxaban are considered reasonable options in clinically stable patients at average risk of bleeding; however, short-acting agents such as argatroban or bivalirudin may be preferred for those with critical illness, increased bleeding risk, or increased potential need for urgent procedures. Also, given the limited available literature, parenteral non-heparin anticoagulants may be preferred in those with life- or limb-threatening thromboembolism. The recommendation is considered conditional, with very low certainty in the evidence about effect. Although limited data exist for any direct-acting oral anticoagulants (DOACs) for this indication, rivaroxaban has the most evidence to support its use. The recommended dosing for each agent is included in Table 1. [1]

A recent review identified 27 studies and case reports regarding the use of DOACs for HIT, which included a total of 104 patients. Overall, the median age of patients was 56 years, and baseline acuity was low or unreported. The most commonly used DOAC was rivaroxaban (60%), followed by apixaban (28%) and dabigatran (12%). Half of patients had the DOAC initiated prior to platelet recovery, and the remaining transitioned from a parenteral anticoagulant after a median of 6 days. The DOACs prevented new and recurrent thrombosis in 98% of cases, and bleeding complications occurred in 3%. Several limitations of use are noted, including a lack of data in several populations (e.g., those with arterial thromboembolism or critical illness) and the inability to use oral agents in those with impaired gut absorption. Although the currently available studies do not support the use of DOACs across all patient populations, the data thus far have been promising. [2]

References:

[1] Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392.
[2] Barlow A, Barlow B, Reinaker T, Harris J. Potential Role of Direct Oral Anticoagulants in the Management of Heparin-induced Thrombocytopenia. Pharmacotherapy. 2019;39(8):837-853. doi:10.1002/phar.2298
Literature Review

A search of the published medical literature revealed 7 studies investigating the researchable question:

What is the data behind utilizing DOACs for HIT and HITT? Are there guidelines that now recommend DOACs for the treatment of HIT or HITT?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-7 for your response.

 

Dosing Guidance from the American Society of Hematology Guidelines*

Drug

 Dosing for HITT Dosing for Isolated HIT

Apixaban

 10 mg twice per day × 1 week, then 5 mg twice per day 5 mg twice per day until platelet count recovery
Dabigatran

150 mg twice per day after ≥5 days of treatment with a parenteral non-heparin anticoagulant

 150 mg twice per day until platelet count recovery

Rivaroxaban

 15 mg twice per day × 3 weeks, then 20 mg once per day 15 mg twice per day until platelet count recovery

*Not approved the treatment of acute HIT. Dosing for treatment of acute HIT is not well established. Suggested dosing is extrapolated from venous thromboembolism and based on limited published experience in HIT. 

HITT: heparin-induced thrombocytopenia complicated by thrombosis; HIT: heparin-induced thrombocytopenia



References:

Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392.

 

An Open-Label, Single-Arm, Pilot Intervention Study to Assess the Efficacy and Safety of Apixaban in Heparin-Induced Thrombocytopenia

Design

Open-label, single-arm, pilot intervention study

N= 30

Objective

 To assess the efficacy and safety of apixaban in the management of heparin-induced thrombocytopenia (HIT)

Study Groups

All participants (N= 30)

Inclusion Criteria

Aged >18 years; received unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH; enoxaparin) for several prophylactic or therapeutic reasons such as nonvalvular atrial fibrillation, deep vein thrombosis (DVT), pulmonary thromboembolism (PTE), and venous thromboprophylaxis; suspected to have progressed HIT

Exclusion Criteria

Active bleeding, hereditary or acquired coagulation disease or bleeding disorder, receiving cytochrome P450 3A4 inhibitor or inducer compounds, severe renal failure (creatinine clearance <25 mL/min), severe liver disease (including Child-Pugh B and C), COVID-19 infection, history of unmodified cerebral aneurysm, intracranial tumor or vascular accident, not participating in another study during the past 30 days, pregnant and lactating women, previous treatment with a non-heparin anticoagulant

Methods

Eligible patients initiated apixaban after discontinuing UFH or LMWH. The dose of apixaban was decided based on the indication for baseline anticoagulant therapy. A dose of 10 mg twice daily for 7 days or until platelet count recovery, whichever is longer, followed by 5 mg twice daily, was used in the treatment of DVT or PE (with or without renal impairment) and also in the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation (NVAF) (without renal impairment). 

In patients who had serum creatinine ≥1.5 mg/dL and either aged ≥80 years or body weight ≤60 kg who received apixaban for the prevention of stroke and systemic embolism in NVAF, the dose was reduced to 5 mg twice daily for 7 days or until platelet count recovery, followed by 2.5 mg twice daily. In a prophylactic setting, we used a dose of 2.5 mg twice a day, unless the patient experienced HIT with thrombosis and received apixaban in the treatment dose of HIT. Duration of apixaban was also dependent on indication and at the treating physician's discretion. Platelet recovery was defined as platelet count ≥150,000/mm3 (or back to baseline if the baseline count was <150,000/mm3).

Duration

Follow-up: 6 months 

Outcome Measures

Primary: incidence of new, progressive, or recurrent thrombosis

Secondary: drug safety, development of hemorrhagic events based on clinical findings, and the occurrence of mortality due to apixaban therapy

Baseline Characteristics

   Total participants (N= 30)

 

Age, years

 57.53  

Female

56.7%  

Reason for initial anticoagulant therapy with UFH or LMWH

DVT prophylaxis

Confirmed DVT

Nonvalvular atrial fibrillation

Confirmed PTE

Suspicion of PTE

Suspicion of PTE 4Ts score

>6

4-5

 

13 (43.3%)

8 (26.7%)

3 (10%)

3 (10%)

3 (10%)

-

24 (80%)

6 (20%)

  

Platelet counts at the time of HIT diagnosis, μL

High-probability group

Moderate-probability group

99,900.0 ± 32,655.3

94,166.6 ± 29,078.1

122,833.3 ± 38,814.5

  

Time of the diagnosis of HIT, days 

 6.6 ± 2.2  

Thrombotic events at the time of HIT diagnosis

New onset of DVT

DVT progression

Nonnecrotizing skin rash at the heparin injection site

 

6 (20%)

3 (10%)

2 (6.6%)

  

Apixaban dosing in study patients

10 mg BID for 7 days, then 5 mg BID

2.5 mg BID

5 mg BID for 7 days, then 2.5 mg BID

 

19 (63.3%)

9 (30%)

2 (6.7%)

  

Results

Endpoint

All participants (N= 30)

p-value

New, progressive, or recurrent thrombosis after apixaban therapy

 None -

Platelet counts after apixaban therapy, μL

High-probability group

Moderate probability group

176,400 ± 30 817.1

171,708.3 ± 30,243.1

195,166.6 ± 27,795.0

0.001

0.09

-

Time of platelet count recovery after apixaban therapy, days

 5.0 ± 1.8 -

Mortality rate during the 6-month follow-up*

 16.7% -

*None of these deaths were related to thromboembolic events, hemorrhagic complications, or apixaban adverse effects.

Adverse Events

Hemorrhagic events after apixaban therapy only occurred in one patient in the high-probability group (3.3%) and none in the moderate-probability group. 

Study Author Conclusions

The study found apixaban to be safe and effective in the treatment of HIT due to the absence of recurrent or new thrombosis and bleeding, and also coincident with platelet recovery. It should be noted that as long as there is not sufficient data from well-designed clinical trial studies to compare the efficacy and safety of apixaban with other FDA-approved parenteral anticoagulants in HIT settings, the application of this approach should be restricted in clinically stable patients.

InpharmD Researcher Critique

The study is limited by its small sample size without a direct comparison to the standard of care for the management of clinically suspected or confirmed HIT. Additionally, exclusion of HIT complicated by life- or limb-threatening thromboembolism may further limit the generalizability of study results to patients with more severe conditions. 



References:

Farasatinasab M, Balouchzehi S, Moghaddam OM, Ansarinejad N, Mohammadi M, Nasiripour S. An Open-Label, Single-Arm, Pilot Intervention Study to Assess the Efficacy and Safety of Apixaban in Heparin-Induced Thrombocytopenia. J Clin Pharmacol. 2022;62(11):1379-1384. doi:10.1002/jcph.2096

 

Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia

Design

Retrospective study

N= 42

Objective

 To identify patients with suspected heparin-induced thrombocytopenia (HIT) who were treated with rivaroxaban and followed for 12 months to assess efficacy and safety

Study Groups

 Study patients (n= 42)

Inclusion Criteria

 Adult patients, developed HIT during treatment with unfractionated heparin or enoxaparin for various indications

Exclusion Criteria

 Renal insufficiency, hepatic impairment, mechanical heart valves, active bleeding

Methods

 Patient data was identified at an Iranian institution for inclusion and analysis. Suspected HIT patients were treated with a dose and duration of rivaroxaban based on the initial indication and preference of the treating physician. 

Duration

Data collection: March 2016 to March 2018

Follow-up: 12 months

Outcome Measures

Primary: occurrence of new symptomatic and objectively confirmed venous or arterial thromboembolism

Secondary: hemorrhagic events, death

Baseline Characteristics

  

Study patients (n= 42)

Age, years

 67.1 ± 14.9

Female

30

Reason for anticoagulation therapy

Deep vein thrombosis (DVT) prophylaxis

Confirmed DVT

Nonvalvular arterial fibrillation

Confirmed pulmonary thromboembolism (PE)

Suspicion of PE

 

20

9

4

4

5

Rivaroxaban dose received

10 mg daily

15 mg BID

15 mg daily

15 mg daily then 20 mg daily

20 mg daily

 

21

3

2

14

2

HIT-associated thrombosis prior to treatment

17

Results

Endpoint

Study patients (n= 42)
New thrombosis

1 (2.3%)

Hemorrhagic events

0

Death*

12 (28.6%)

*No deaths were due to thrombosis, hemorrhage, or adverse events of rivaroxaban. Reasons for death include sepsis, severe heart failure, and cancer. 

Adverse Events

See results. 

Study Author Conclusions

 Rivaroxaban is a particularly valuable treatment option in developing countries, where there are issues of cost and availability of approved alternative agents.

InpharmD Researcher Critique

 The study was focused in Iran with a different healthcare climate compared to the United States. The small sample size and lack of a comparator group make it difficult to conclude if rivaroxaban is similar to other post-HIT management strategies.



References:

Farasatinasab M, Zarei B, Moghtadaei M, Nasiripour S, Ansarinejad N, Zarei M. Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia. J Clin Pharmacol. 2020;60(10):1362-1366. doi:10.1002/jcph.1635

 

Dabigatran as a Treatment Option for Heparin-Induced Thrombocytopenia

Design

Single-center, retrospective chart review and prospective follow-up

N= 40

Objective

To evaluate the efficacy and safety of dabigatran in patients with heparin-induced thrombocytopenia (HIT) 

Study Groups

All patients (N= 40)

Inclusion Criteria

Adult patients who received dabigatran for the management of suspected HIT based on 4Ts (thrombocytopenia, timing of platelet count drop, thrombosis or other sequelae, and other causes of thrombocytopenia) scores 

Exclusion Criteria

Patients with severe renal insufficiency (creatinine clearance <15 mL/min)​, hepatic impairment, mechanical heart valves, active bleeding, and extremes of weight (<50 kg and >120 kg)

Methods

Medical records of patients who received dabigatran for the management of suspected HIT after administration of unfractionated heparin or low molecular weight heparin were reviewed. Patients with suspected HIT received dabigatran 110 mg twice daily if they had normal renal function, or 75 mg twice daily if their renal function was impaired (creatinine clearance 15–30 mL/min). Durations of dabigatran use were based on the initial indication, which was determined by the treating physician. Platelet count recovery was defined as a count ≥150,000 mL-1, or back to the baseline if the baseline counts were <150 000 mL-1. 

Duration

Chart review period: February 2014 to February 2016

Prospective follow-up: 12 months

Outcome Measures

Primary: incidence of new symptomatic and objectively confirmed venous or arterial thromboembolism

Secondary: development of hemorrhagic events based on clinical findings, platelet count, and mortality rate

Baseline Characteristics

  

All patients (N= 40)

  

Mean age, years

 69.98  

Female

60%  

Reason for anticoagulant therapy

DVT prophylaxis 

Confirmed DVT 

Nonvalvular arterial fibrillation

Coronary artery bypass graft 

Confirmed pulmonary thromboembolism

Suspicion pulmonary thromboembolism

 

32.5%

27.5%

22.5%

7.5%

7.5%

2.5%

  

4Ts score

≥ 6

4-6

 

82.5%

17.5%

  

Dabigatran dose

110 mg twice daily

75 mg twice daily

 

82.5%

16.6%

  

Mean baseline platelet count, mL-1

213,550

  

Results

Endpoint

All patients (N= 40)

p-Value

Thromboembolic events

 1 (2.5%)   -

Bleeding events

 2 (5%) -

Platelet counts

After dabigatran administration, mL-1

Time to recover after dabigatran administration, days 

 

157,550 ± 85,688

7.4 ± 4.3

 

<0.001 

-

Mortality rate§

20%

-

§The mortality rate was not related to thromboembolic events, hemorrhagic complications, or dabigatran adverse reactions

Bleeding episodes were minor in the form of skin ecchymosis and resolved spontaneously without complications

Adverse Events

Not disclosed

Study Author Conclusions

Based on our findings, dabigatran could be considered a safe and effective agent in the management of HIT, particularly in developing countries, where there could be issues with the cost and availability of other agents recommended for this condition. Further studies are needed to validate our findings.

InpharmD Researcher Critique

 The study is limited by its single-center, retrospective design, and small sample size. 



References:

Nasiripour S, Saif M, Farasatinasab M, et al. Dabigatran as a Treatment Option for Heparin-Induced Thrombocytopenia. J Clin Pharmacol. 2019;59(1):107-111. doi:10.1002/jcph.1300

 

Evaluation of the use of direct oral anticoagulants for the management of heparin‐induced thrombocytopenia

Design

Single-center, retrospective chart review

N= 26

Objective

To describe the use of direct oral anticoagulants (DOACs) for heparin‐induced thrombocytopenia (HIT) at the study institution, including patients treated with DOAC monotherapy

Study Groups

All participants (N= 26)

Inclusion Criteria

Aged ≥ 18 years and received a DOAC for the treatment of HIT

Exclusion Criteria

 Not specified 

Methods

Patients' electronic health records were retrospectively reviewed to collect relevant baseline information and clinical courses. Venous thromboembolism (VTE) dosing of DOACs refers to the package insert dosing for initiation of either apixaban or rivaroxaban for those being treated for newly diagnosed VTE; apixaban 10 mg BID for 7 days, followed by 5 mg BID and rivaroxaban 15 mg BID for 21 days followed by 20 mg once daily.

At the study institution, a HIT diagnosis was defined as either (1) positive heparin/platelet factor-4 (PF4) optical density (OD) ≥ 0.4 and a positive serotonin-release assay (SRA) with at least 20% serotonin release (with low dose heparin at 0.1 U/mL in the serum) together with inhibition of serotonin release (< 20%) with high dose heparin (100 U/mL) (2) a positive heparin/PF4 (OD ≥ 0.4) with or without positive SRA and 4T score > 5 as documented by the pharmacist/Hematology team (3) a positive SRA with or without positive heparin/PF4.

Duration

From January 2017 to October 2020

Outcome Measures

Major: DOAC agent selection and dose, timeframe from HIT diagnosis to DOAC initiation, percentage of patients who received parenteral therapy prior to DOAC initiation

Minor: time to platelet recovery defined as ≥ 150 × 109/L or ≥ baseline if baseline platelets were < 150 × 109/L, percentage of patients achieving platelet recovery within 30 days, new or worsening thrombosis within 30 days of diagnosis, and the length of intensive care unit (ICU) and hospital stay

Baseline Characteristics

  

All participants (N= 26)

  

Age, years

 65.5 ± 9.8  

Female

34.6%   

Creatinine clearance, mL/min

 72.8 ± 33  

Past medical history

Cardiovascular disease

History of VTE

Previous bleed

Non-valvular atrial fibrillation

Active malignancy

 

11.5%

3.8%

7.7%

15.4%

11.5%

  

Concomitant medicaitons

Aspirin only

Dual antiplatelet therapy (DAPT)

Anticoagulation

 

34.6%

3.8%

19.2%

  

Indication for initial anticoagulation

VTE prophylaxis

VTE treatment

Acute coronary syndrome

Atrial fibrillation

Antiphospholipid antibody syndrome

 

34.6%

42.3%

7.6%

19.2%

3.8%

  

Anticoagulant attributed to HIT

Heparin

Low molecular weight heparin

 

92.3%

7.6%

  

Results

Endpoint

 All participants (N= 26)

 

Major endpoints

DOAC initiation

Initial treatmenta

Platelet recovery

Platelets trending up

At discharge

 

 

5 (19.2%)

11 (42.3%)

7 (26.9%)

3 (11.5%)

  

Initial parenteral anticoagulation

Bivalirudin

Argatroban

Fondaparinux

21 (80.8%)

18 (69%)

2 (8%)

1 (4%)

  

Duration of parenteral anticoagulation, days (interquartile range [IQR])

 7 (4 to 18)  

Initial DOAC

Apixaban VTE dosing

Apixaban 2.5 mg twice daily

5 (19.2%)

4 (80%)

1 (20%)

  

Minor endpoints

Platelet recovery

HIT (n= 10)

HIT with thrombosis (HITT; n= 16)

 

23 (88.5%)

9 (90%)

14 (87.5%)

  

Days to platelet recovery from HIT diagnosis

HIT (n= 9)

HITT (n= 14)

5 (2.8 to 8.3)

5 (5 to 6)

5 (2 to 9.8)

  

New or worsening thrombosis within 30 days

 0  

Hospital length of stay (days)

19 (10.3 to 31.3)

  

ICU length of stay (days)

HIT (n=6)

HITT (n = 7)

17 (8 to 30)

12.5 (6.8 to 37.8)

25 (8 to 30) 

  

aApixaban only DOAC used as initial treatment

Time to platelet count recovery by treatment strategy appeared to be similar between initial treatment with DOAC (n= 5; 6 days; IQR 2.3 to 14.5) and initial parenteral treatment (n= 18; 5 days; IQR 2.8 to 8.3). 

All patients managed with a DOAC as initial treatment achieved platelet recovery within 30 days of HIT diagnosis.

Adverse Events

 Major safety endpoint: no bleeding was reported (defined by the International Society of Thrombosis and Haemostasis)

Study Author Conclusions

At this institution, the use of DOACs to treat HIT demonstrated efficacy and safety in a small number of patients and allowed platelet recovery with no evidence of new or progressive thrombosis. Apixaban, at the therapeutic dose to treat thrombosis, was prescribed most frequently with a therapeutic dose of rivaroxaban and apixaban 5 mg BID in the remaining cohort. The majority of patients were treated with a DOAC after platelet recovery with a direct thrombin inhibitor (DTI). Platelet recovery was achieved in all patients started on DOAC as initial treatment, similar to those receiving a parenteral DTI as their initial treatment.  

InpharmD Researcher Critique

The current study is limited by its single-center and retrospective design, in addition to a lack of formal statistical analyses for clinical outcomes. Use of DOAC as the initial treatment for HIT remained uncommon in practice, pending evaluation in larger prospective trials. 



References:

Albuloushi A, Rhoten M, Kelly J, Sylvester KW, Grandoni J, Connors JM. Evaluation of the use of direct oral anticoagulants for the management of heparin-induced thrombocytopenia. J Thromb Thrombolysis. 2022;54(4):597-604. doi:10.1007/s11239-022-02705-6

 

Direct acting oral anticoagulants for the treatment of suspected heparin-induced thrombocytopenia

Design

Retrospective cohort study

N=12

Objective

To evaluate the efficacy and safety of direct oral anticoagulant (DOAC) therapy in hospitalized patients with suspected heparin-induced thrombocytopenia (HIT)

Study Groups

Apixaban (n= 9)

Rivaroxaban (n=3)

Inclusion criteria

An intermediate or high pretest probability for HIT (4T score≥4) and a positive IgG-specific anti-PF4/heparin complex assay

Exclusion criteria

Negative serotonin release assay, previous history of HIT prior to admission or were admitted for less than 48 hours

Methods

This was a retrospective review of patients with HIT who were given either apixaban or rivaroxaban between 2013 and 2017 at a single health system. Seven apixaban-treated patients received a dose of 5 mg twice daily, 1 received a dose of 10mg twice daily and 1 received a dose of 2.5mg twice daily. All rivaroxaban-treated patients received 15 mg twice daily.

Duration

Average treatment duration while hospitalized: 9.33 days (range 1-32 days)

Outcome Measures

Composite of newly diagnosed venous or arterial thromboembolism, gangrene, or amputation due to critical limb ischemia during hospitalization

Baseline Characteristics

  

All patients (n=12)

Age years, (range)

 66.5 (40-85)

Female

 6 (50%)

Platelet nadir, x109/L (range)

 57.6 (12-91) 

Time on DOAC prior to discharge, days (range)

 9.3 (1-32)

Results

 

All patients (n=12)

HIT related thrombosis

0

Major bleeding post DOAC initiation

0

Number of patients who achieved platelet recovery while receiving DOAC therapy

12

Time to platelet recovery, days (range)  

 7.42 (3-14)

Recurrent thrombosis 

0

Bleeding 

0

Adverse Events

No patients experienced a thrombotic-related event or major bleed while receiving DOAC therapy.

Study Author Conclusions

In this small retrospective study of adult patients treated for acute HIT, treatment with DOAC therapy was not associated with in-hospital thrombotic or hemorrhagic events.

InpharmD Researcher Critique

Due to the small sample size and retrospective nature of the trial, the results of the present study should be interpreted with caution. Additionally, as patients were only followed during the course of their hospital stay the long-term outcomes could not be assessed.

 

References:

Davis KA, Davis DO. Direct acting oral anticoagulants for the treatment of suspected heparin-induced thrombocytopenia. Eur J Haematol. 2017;99(4):332-335.

 

Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study

Design

Prospective, cohort study

N= 12

Objective

To evaluate the efficacy and safety of rivaroxaban for the treatment of heparin‐induced thrombocytopenia (HIT)

Study Groups

Rivaroxaban for HIT positive patients (n=12)

Inclusion criteria

Patients with confirmed or suspected HIT

Exclusion criteria

 Pregnant or nursing, mechanical heart valve, severe renal insufficiency, hepatic disease, and clinically significant active bleeding within the last six months
Methods 

Eligible participants received rivaroxaban 15 mg twice daily until platelet recovery (or until at least day 21 if they had acute thrombosis [HITT]), then stepped down to rivaroxaban 20 mg daily until day 30.

The study was terminated early because of poor recruitment, but after enrolling the minimum expected number of HIT-positive participants.

Duration

30 days

Outcome Measures

 Venous thromboembolism, bleeding, mortality

Baseline Characteristics

  

Rivaroxaban for HIT (n=12)

Age, years

 76.5

Male

 7 (58.3%)

Results

 

Rivaroxaban for HIT (n=12)

Venous thromboembolism§

 1 (8.3%)

Bleeding

 1 (8.3%)

Mortality*

 4 (33.3%)

§The venous thromboembolism episode was an extension of previously documented apheresis catheter-related arm deep vein thrombosis. An ultrasound was not performed at study entry so it is possible that the extension occurred prior to the start of rivaroxaban.

The incidence of bleeding occurred 9 days after holding rivaroxaban

*Mortality was not related to the study drug

Adverse Events

 N/A

Study Author Conclusions

Rivaroxaban is a promising agent for the treatment of HIT. The challenges of conducting large methodologically rigorous trials are likely to be prohibitive; however, observational data will accumulate over time, as was the case with fondaparinux, which is frequently used to treat HIT off‐label. Furthermore, properties such as oral administration and a lower cost would give rivaroxaban important advantages over fondaparinux.

InpharmD Researcher Critique

This study was underpowered. The one event seen could have possibly occurred prior to the start of the study drug.

 

References:

Linkins LA, Warkentin TE, Pai M, et al. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016;14(6):1206-10.