Do patients that have a history of drug abuse or alcohol abuse need higher doses of heparin?

Comment by InpharmD Researcher

Published evidence addressing whether higher heparin doses are needed in patients with a history of drug or alcohol abuse is limited. One comparative study of patients with and without opioid use disorder (OUD) undergoing percutaneous coronary intervention (PCI) demonstrated that after receiving the same weight-based dose of heparin, the OUD group had significantly shorter activated clotting times (ACTs) at 2 and 30 minutes, suggesting the potential need for higher doses of heparin in PCI; however, there were no significant differences in PT, PTT, INR, and platelet counts. A small retrospective study evaluating heparin requirements in patients with a history of intravenous drug misuse (IVDM) found a possible association of reduced antithrombin activity with this patient population, with the authors suggesting that anti-Xa monitoring or higher initial heparin infusion rates may be considered to achieve therapeutic anticoagulation. Overall, the evidence base is small, with the few available studies subject to methodological limitations and potential confounding. Additional robust trials are needed to confirm these findings.
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Do patients that have a history of drug abuse or alcohol abuse need higher doses of heparin?

Level of evidence

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


Please see Tables 1-2 for your response.

Do Opioid Addicts Require Higher Doses of Heparin During Percutaneous Coronary Intervention?
Design

Comparative study

N= 107
Objective To compare the effect of heparin on activated clotting time (ACT) between opioid addicts and non-addicts prior to and during PCI
Study Groups

Opioid addicts (n= 50)

Non-addicts (n= 57)
Inclusion Criteria Patients with ischemic heart disease (IHD) scheduled for elective PCI
Exclusion Criteria Underlying diseases affecting coagulation (either hereditary such as hemophilia or acquired such as liver failure in chronic hepatitis), drug history of warfarin, glycoprotein IIb/IIIa inhibitors, or other anticoagulants, any coagulation disorder observed in initial lab results, emergency PCI
Methods Patients received 100 IU/kg heparin at the beginning of PCI. ACT was measured at 2 and 30 minutes using the ACT plusTM device.
Duration Study conducted in 2018
Outcome Measures

Primary: ACT at 2 and 30 minutes, Change in ACT

Secondary: PT, PTT, INR, Platelets, Correlation of ACT with drug history of aspirin and cigarette smoking
Baseline Characteristics   Opioid addicts (n = 50) Non-addicts (n = 57) p-value
Age, years 58.44 ± 10.78 58.84 ± 11.38 0.852
Male 47 (94.0%) 50 (87.7%) 0.331
Weight, kg 65.86 ± 12.84 71.37 ± 13.06 0.094
Heparin, IU 6,635.42 ± 1,253.33 7,215.09 ± 1,338.68 0.058

Comorbidities

Hypertension

Diabetes

Hyperlipidemia

 

18 (36.0%)

10 (20.0%)

5 (10.0%)

 

30 (52.6%)

11 (19.3%)

15 (26.3%)

 

0.084

0.927

0.031

Drug history

Aspirin

Clopidogrel

 

24 (48.0%)

13 (26.0%)

 

37 (64.9%)

23 (40.4%)

 

0.078

0.117

Smoking

Cigarette

Hookah

 

25 (50.0%)

8 (16.0%)

 

7 (12.3%)

6 (10.5%)

 

< 0.001

0.402
Results   Opioid addicts (n= 50) Non-addicts (n= 57) p-value
ACT at 2 min, sec 292.14 ± 71.34 412.98 ± 150.83 < 0.001
ACT at 30 min, sec 213.80 ± 49.50 255.23 ± 64.26 < 0.001
Change in ACT, sec 78.34 ± 58.39 157.75 ± 152.23 0.002
PT, sec 13.35 ± 1.08 13.29 ± 0.76 0.718
PTT, sec 31.10 ± 5.01 30.13 ± 4.32 0.246
INR 1.08 ± 0.14 1.07 ± 0.11 0.798
Platelet, ×103/µL 208.61 ± 64.48 223.44 ± 58.31 0.260
ACT at 2 min was directly correlated with drug history of aspirin in opioid addicts (p= 0.031) and inversely correlated with cigarette smoking in non-addicts (p= 0.023).
Adverse Events No specific adverse events reported.
Study Author Conclusions Opioid addicts may require higher doses of heparin in PCI to prevent thrombotic complications compared to non-addicts.
Critique The study provides valuable insights into the differential heparin requirements for opioid addicts during PCI. However, the small sample size and potential underreporting of opioid use due to social stigma may limit the generalizability of the findings. Additionally, the lack of a standardized measure for opioid consumption could affect the accuracy of the results.

 

Table 1 References:
[1] Afaghnia T, Nasim-Tajik M, Boushehri E, Nikparvar M, Gharibzade A, Farshidi H. Do opioid addicts require higher doses of heparin during percutaneous coronary intervention? Addict Healt. 2021;13(4). doi:10.22122/ahj.v13i4.1198
Evaluation of heparin infusion rates in patients with intravenous drug misuse
Design

Multicenter, retrospective study

N= 41
Objective To evaluate the hypothesis that patients with a history of intravenous drug misuse (IVDM) initiated on weight-based heparin infusions require higher than expected infusion rates to achieve therapeutic activated partial thromboplastin time (aPTT)
Study Groups All patients (N= 41)
Inclusion Criteria Patients ≥18 years old with a recent (within the past six months) documented history of IVDM who received treatment with a weight-based heparin infusion between 10/1/2015 and 9/30/2020
Exclusion Criteria Pregnant women; women of child-bearing age without a negative pregnancy test on file; non-continuous heparin infusion; heparin infusion not continued for at least 48 consecutive hours; initiated on heparin infusion at a facility outside of the seven identified acute care sites
Methods A retrospective chart review was conducted. Patients were identified using ICD9 and ICD10 codes. All heparin infusions were initiated at a rate of 18 units/kg/hr, then titrated per institutional heparin infusion protocols.
Duration 10/1/2015 to 9/30/2020
Outcome Measures

Primary: Therapeutic heparin infusion rates in patients with recent IVDM

Secondary: Average time to reach therapeutic aPTT, incidence of moderate-to-severe bleeds per ISTH criteria
Baseline Characteristics   All patients (N= 41)
Age, years 35 ± 9.4
Female 23 (56.1%)
Total body weight, kg 74.2 ± 21.6
CrCl (mL/min) ≥ 90 31 (75.6%)

Indication for heparin infusion

Acute DVT

Acute PE

History of DVT/PE

 

20 (49%)

14 (34%)

7 (17%)

Proximity of IVDM to hospital admission

< 48 h

≤ 1 week

> 1 week

< 1 month

 

18 (43.9%)

11 (26.8%)

6 (14.6%)

6 (14.6%)

Urine toxicology results

Positive

Opiates

Oxycodone

Cocaine

Amphetamines

Benzodiazepines

Barbituates

THC

Tricyclic antidepressants

Fentanyl

Methadone

Negative

Not obtained

 

29 (70.7%)

14 (34%)

4 (9.8%)

10 (24.4%)

12 (29.3%)

2 (4.9%)

1 (2.4%)

5 (12.2%)

1 (2.4%)

1 (2.4%)

1 (2.4%)

4 (9.7%)

8 (19.5%)
Results   All patients (N= 41)
Initial infusion rate, units/kg/hr 18 ± 0
Lowest infusion rate when therapeutic, units/kg/hr 25 ± 7.8
Highest infusion rate when therapeutic, units/kg/hr 28.7 ± 6.6
Maintenance infusion rate, units/kg/hr 27.6 ± 7.1
Number of patients who achieved therapeutic aPTT 39 (95.1%)
Time to reach therapeutic aPTT, hr 38.5 ± 26.4
Adverse Events

Despite increased heparin dosing requirements, patients did not experience a clinically significant increase in moderate-to-severe bleeds as defined by the ISTH.

One patient experienced a gastrointestinal bleed resulting in a hemoglobin decrease of more than 2 g/dL.
Study Author Conclusions The findings in this study demonstrate a possible clinical association of the reduced antithrombin activity previously described in opiate misusers. To efficiently achieve therapeutic anticoagulation, it may be appropriate to consider use of heparin antiXa monitoring in place of aPTT or utilization of increased initial heparin infusion rates.
Critique The study highlights a significant gap in understanding the pharmacokinetics of heparin in patients with a history of IVDM. However, the retrospective design limits the ability to control for confounding factors, and the lack of a control group limits the ability to draw definitive conclusions. The study's findings are not generalizable beyond the specific health system and geographic location. Future studies should include a larger sample size, a control group, and be prospective in nature to validate these findings.

 

Table 2 References:
[2] Barga K, Smith A, Faherty M, Crawford K. Evaluation of heparin infusion rates in patients with intravenous drug misuse. J Thromb Thrombolysis. 2022;53(4):959-964. doi:10.1007/s11239-021-02615-z