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Indo American Journal of Pharmaceutical Research, 2015 ISSN NO: 2231-6876

ENOXAPARIN INDUCED LOCAL HYPERSENSITIVITY REACTIONS -A RARE CASE

REPORT

Dr. M Sureswara Reddy1,

P Venkata Ramana2,

Gangula Amareswara Reddy2 ,M Venkata Subbaiah

2,

B. Narasimha2

1 MD, General Medicine, Associate Professor, Rajiv Gandhi institute of medical sciences, Kadapa, India.

2P Rami Reddy Memorial College of Pharmacy, Kadapa, Andhra Pradesh, India – 516003.

Corresponding author

Amareswara Reddy Gangula

Pharm D Intern,

P Rami Reddy Memorial College of Pharmacy (PRRMCP),

Rajiv Gandhi Institute of Medical Sciences (RIMS),

Kadapa, Andhra Pradesh, India

amarpdtr@gmail.com

+91 9502422806

Copy right © 2015 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical

Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ARTICLE INFO ABSTRACT

Article history

Received 15/03/2015

Available online

31/03/2015

Keywords

Enoxaparin,

Local Hypersensitivity

Reaction,

ADR,

VTED,

LMWH,

Causality Assessment,

ECG.

Enoxaparin is extensively used in the treatment of venousthrombo-embolic disease (VTED)

which inhibits blood clotting inside the blood vessels by the inhibition of factor Xa activity

through antithrombin. Local hypersensitivity reactions are one of the rare adverse drug

reactions (ADR) of enoxaparin which may lead to hospitalization and excessive burden to the

patient. A 72 years male patient was admitted in general medicine department with

retrosternal pain even at rest and was diagnosed with unstable angina pectoris. He was

administered with anti-coagulantEnoxaparin 0.4ml (40 I.U)subcutaneouslyalong with other

supportive medications. Patient have developed severe local hyper sensitivity reactions like

erythema,pain,swelling,irritation at the site of injection, and suspected as an ADR of

Enoxaparin and immediately drug was withdrawn, then it was confirmed through causality

assessment and this ADR have shown +ve for rechallenge;patient was fallowed for

improvement and the symptoms especially swelling and irritations were not subsidedeven on

9th

day. By this case study we strongly recommend the testingof drug sensitivity before

initiating Enoxaparin therapy,and need to collect past history comprehensively for safe and

effective outcome of therapy.

Please cite this article in press as Dr. M Sureswara Reddy et al. Enoxaparin Induced Local Hypersensitivity Reactions -A Rare

Case Report. Indo American Journal of Pharm Research.2015:5(03).

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INTRODUCTION

Low molecular weight heparins (LMWH) are fragments of standard commercial grade heparin produced by either chemical

or enzymatic de-polymerization. LMWHs are approximately one-third the sizeof heparin. Like heparin, which has a mean molecular

weight of 15,000 Daltons(Da)(range 3000 to 30,000 Da), LMWHs are heterogeneous in size with a mean molecular weight of 4000 to

5000 Da (range 1000 to 10,000 Daltons).Enoxaparin is presently used in the prophylaxis and treatment of stroke, deep venous

thrombosis, myocardial infarction, pulmonary thromboembolism. When compared with heparin, nowadays enoxaparin is commonly

usedinstead of heparin especially not suitable for chronic as it is associated with serious adverse effects like bleeding,

thrombocytopeniaand osteoporosis,usage it require monitoring of activated partial thromboplastin time(aPTT)1. But LMWHs have

higher subcutaneous bio-availability,longer duration of action and do not require aPTT monitoring, and the adverse effects of LMWH

are less when compared with normal unfractionated heparin (UFH), and the same has been assessed in a number of experimental

studies2,3

.The majorityof information publishedin various studies suggests that the skin reactions are usually benign in nature 4,5

.Many

case reports have been published which showed the adverse reactions taking place at local and far from the site of injection6.

This is a case report of 72year male patient admitted with unstable angina and experienced local hypersensitive reactions at

the subcutaneous site of enoxaparin injection.

Case

A 72 years old man was admitted in general medicine ward with chief complaints of chest pain since three days. The pain

was radiating to left shoulder followed by neck region. He revealed that he had experienced profound sweating and nausea

feeling.Patient had history of similar retrosternal pain one week back. He was a known hypertensive patient since one year, but is on

irregular treatment. On general examination, he was conscious and coherent, Pulse rate – 78 beats per minute, BP – 140/70 mm of Hg,

CVS – S1S2+ve, CNS – No abnormality was observed. The patient’s ECG report showedslight ST depression and t-wave inversion

(Figure1)

Figure 1: ECG showing slight ST depression and t-wave inversion.

Based on the subjective and objective evaluation he was diagnosed with unstable angina. Patient was started treating with

oral anti-anginal drug (Sorbitrate 5 mg sublingually), oral antiplatelet drugs (Ecospirin 150 mg + Clopitab 75 mg once a day),

subcutaneous anti coagulant Enoxaparin 40 IU b.d, and oral anti hyperlipidemic drug (Atorvastatin 20 mg od HS), parenteral

antibiotic (Augmentin 1 gram iv bd), parenteral antiulcerative (Pantoprazole 40 mg iv bd).

Upon administration of injection Enoxaparin through subcutaneous route, within few minutes the patient experienced severe

irritation at the site of injection and was associated with erythema, followed by pain and swelling.

Figure 2:Readministration of Enoxaparin Through Subcutaneous Route.

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Figure 3: After the re-administration of subcutaneous Enoxaparin.

ADR management:

In the management of ADR, first the drug was withdrawn from the therapy after rechallenge and symptoms were treated with

oral antihistamines (CPM) and topical preparations (Corticosteroids).

Analysis of ADR:

Rechallenge:

Patient had experienced hypersensitivity reactions like erythema and swelling on first time administration of enoxaparin,

which was shown in circle in Figure 2 and 90 % of symptoms were subsided after withdrawal of the drug and on subsequent

administration of the same drug in same route, produced the same reactions with higher intensity which was shown in circle in Figure

2&3and the patient was not recovered completely from the symptoms of the ADR even after the 9 th

day of Enoxaparin administration.

Causality assessment: Causality assessment should be performed to find the time relationship between the ADR and the suspected

drug. We have performed causality assessment by using standard scales like, WHO causality assessment scale, Naranjo’s scale and

Karch - Lasagna scale, results were shown in the Table 1

Table 1: Causality assessment of the suspected ADR.

ADR SCALE WHO-UMC NARANJO’S KARCH&LASAGNA

ASSESMENT Certain Definite Definite

Further analysis was performed to know the other parameters like Severity, Preventability and predictability of the suspected

ADR,shown in Table 2.

Table 2: Analysis of observed ADR.

DISCUSSION Ischemic heart disease includes both angina pectoris and myocardial infarction. Angina pectoris is due to imbalance between

myocardial oxygen supply and demand. Whereas myocardial infarction is a condition in which there will be death of myocardial cells

due to deficiency of oxygen supply. Generally angina pectoris will progress to myocardial infarction if not treated. Myocardial

infarction is a condition in which primarily it needs within six hours administration of plasminogen activators for breaking thrombus

present in the coronary arteries. Then for preventing further thrombus formation anti-coagulants will be used, more commonly low

molecular weight heparins. In our case injection enoxaparin was given in unstable angina prophylactically for preventing thrombus

formation in the coronary vessels. Generally it will be given through sub cutaneous route and it does not produce any serious adverse

reactions except blood dyscrasias. In our case, maybe the patient might had an allergic drug reactionresulting in irritation, erythema (4

cms), pain and swelling. The hypersensitive reaction was seen instantly after the administration of enoxaparin and not improved after

the drug was stopped. Hehas not experienced similar type of allergic reaction in his past and there were no other causes for

manifestation of irritation at those particular sites.The hypersensitive reaction appeared as local skin changes usually at the site of

injection. Very little has been known about such reactions but few scientists believe that heparins may bind to subcutaneous or dermal

proteins and may trigger hypersensitivity reaction.

SEVERITY ASSESSMENT Moderate Level 3

PREVENTABILITY Not Preventable

PREDICTABILITY Unpredictable

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CONCLUSION

Better vigilance is necessary for implementation of safe and effective treatment for each individual patient. In order to

prevent local hypersensitivity reactions of this drug, creating awareness, recognition of the problem, and careful management of all

patients who receive this medication are essential. As like penicillins, this drug is also need to be tested with little dose before the

therapy started.

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heparin therapy in a patient under chronic coumarin anticoagulation. J Eur Acad Derma-tol Venereol 2006; 20(3): 327-30.

4. Nadir Y, Mazor Y, Reuven B, Sarig G, Brenner B, Krivoy N. A fatal case of enoxaparin induced skin necrosis and thrombophilia.

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