Cardiovascular Journal of Africa: Vol 27 No 3 (May/June 2016)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016

AFRICA

15th day after admission and revealed resolution of the thrombi

in the RCA (Fig. 4). The patient was discharged and received

medical therapy, including aspirin, clopidrogel and a statin

instead of stent implantation. She had an uneventful recovery

and there were no cardiac events during clinical follow-up of

one year.

Discussion

For over 80 years, heparin has been used clinically as an

anticoagulant.

Thrombocytopaenia as a result of heparin

therapy was first described in the late 1960s.

The HIT syndrome

is characterised by thrombocytopaenia and thrombotic

manifestations after exposure to heparin.

Administration of

heparin products is often in the setting of thrombosis or

pro-thrombotic stimuli.

The initial steps of HITS involve patient exposure to

heparin, followed by initial formation of the IgM antibody,

and development of IgG antibodies over four to 14 days.

IgG

antibodies activate the platelets and release the contents of

platelet granules. When platelet factor 4 (PF4) is released, it

binds to heparin, resulting in a conformational change in PF4.

The IgG antibodies and PF4–heparin become a ‘foreign antigen’,

which can be immunogenic.

8,9

The activated platelets secrete

more PF4, feeding back to create more antigen and aggregate,

which become procoagulant. Thrombin is then generated and

platelet–fibrin thrombi are formed.

When HITS appears to present with bleeding, this is usually

the result of a thrombotic complication.

For example, cerebral

venous thrombosis causes increased venous congestion, and

it may similarly manifest as intracranial haemorrhage. The

thrombotic complications of HIT manifest as arterial or venous

thromboses. Venous thrombotic events predominate over arterial

events, and less common manifestations are necrotising skin

lesions at the heparin injection sites.

The severity of thrombocytopaenia is associated with higher

risk of HIT-related thrombosis. In some HIT cases, there may

be life-threatening complications, such as deep-vein thrombosis,

pulmonary embolus, myocardial infarction, cerebral sinus

thrombus, stroke, adrenal vein thrombosis, limb gangrene and

acute limb ischaemia.

8,12

The diagnosis of HITS includes a 50% fall in platelet count,

beginning between five and 14 days after initial exposure to

heparin of any dose or type, and detection of the HIT antibody

against the PF4–heparin complex is necessary.

PF4–heparin

antibodies have been widely used for the diagnosis of HITS. The

diagnostic criteria of HIT include thrombocytopaenia during

heparin therapy, resolution of thrombocytopaenia after cessation

of heparin, exclusion of other causes of thrombocytopaenia and

confirmation of heparin-induced antibodies.

Thereare two types inHITS.

HITtype1 isnon-immunological

and causes activation and aggregation of platelets, and eventually

results in thrombocytopaenia. The degree of thrombocytopaenia

does not fall below 100 000 cells/

l. It appears during the first

hours of heparin administration and thrombosis is not observed.

HIT type 2 is usually defined as a relative decrease in platelet

counts to less than 50% of baseline or an absolute decrease to

less than 100 000 cells/

l, typically five to 10 days after initiation

of heparin therapy, a pattern indicative of the immunological

aetiology of the condition.

Compared to UFH, LMWH shows better outcomes, not

only in thromboembolic events but also in complications such

as HITS. Although antithrombotic therapy with LMWH is

known to be safer than therapy with UFH, enoxaparin-induced

thrombocytopaenia can occur.

Even though enoxaparin-induced

thrombocytopaenia occurred less often than HITS in one study,

the clinical manifestations of both were similar.

It is a general principle that for patients with suspected or

confirmed HITS, all forms of heparin should be stopped and

transfusion of platelet concentrate should not be considered

unless thrombocytopaenia is life-threatening, or when the

patient undergoes invasive procedures with high risk of bleeding,

because the administered platelets would cause thromboembolic

complications to develop or it would aggravate them.

13,14,18

Anticoagulation with an alternative non-heparin anticoagulant

should be commenced.

The direct thrombin inhibitors (DTIs) such as argatroban,

bivalirudin and lepirudin are effective in the treatment of

HIT-induced thromboembolismandas alternative anticoagulants

for thrombosis prophylaxis in patients diagnosed with HIT.

15,16,18

When DTIs are not available, factor Xa inhibitors such as

fondaparinux should be administered. The binding of factor Xa

inhibitors to antithrombin inhibits factor Xa, thus decreasing the

rate of thrombin generation.

In this case, we did not recognise any of these pathognomonical

signs of enoxaparin-induced thrombocytopaenia, except a

drop in platelet count and nasal bleeding after 10 days of

anticoagulation therapy. The platelet count was normalised

within days of discontinuation of enoxaparin.

Both the clinical situation of the patient and the medical

treatment, including intracoronary abciximab, aspirin and

clopidogrel could have been a cause of thrombocytopaenia,

but the fact that the platelet count normalised after stopping

enoxaparin, and the presence of anti-PF4–heparin antibodies

suggested HITS. We diagnosed enoxaparin-induced

thrombocytopaenia because of the clinical features, the patient’s

heparin-naïve state and the laboratory finding of antibodies

against PF4 and heparin complexes.

Another factor was the administration of aspirin and

clopidogrel, which changed the activation of platelet aggregation

in response to the stimulus of anti-PF4–heparin antibodies,

although dual antiplatelet therapy with aspirin and clopidogrel

neither treats HITS, nor aggravates HIT to form a thrombotic

complication. This may explain why there was only nasal

bleeding with the absence of any thrombotic complications in

this patient, and it may have affected her prognosis.

We treated this patient with medication instead of stenting

because of her large RCA diameter of more than 6 mm. The

patient received dual antiplatelet agents, including 100 mg of

aspirin and 75 mg of clopidogrel per day, and there were no

other major adverse cardiac events during clinical follow up.

There are a few reports of enoxaparin-induced thrombo-

cytopaenia in the literature but no reports however on enoxaparin-

induced thrombocytopaenia during medical treatment of acute

myocardial infarction.

Conclusion

We report our experience with enoxaparin-induced

thrombocytopaenia during medical treatment of acute