Coronary thrombosis: In vivo, ex vivo and in vitro

Abstract

Acute stent thrombosis remains one of the most important concerns in clinical cardiology. The mechanism is not fully understood but a prothrombotic state is a key component. We describe a case of acute stent thrombosis, within an hour of rescue angioplasty, despite use of full dose fibrinolytic (reteplase) and antiplatelet therapy (aspirin and clopidogrel). Risk of acute stent thrombosis was predicted an hour earlier, when the patient was clinically well, by a novel near-patient test of thrombotic and thrombolytic status (in vitro). Subsequent stent thrombosis was visualised angiographically (in vivo) and confirmed by extraction of the thrombus (ex vivo). The near-patient test sensitively detected reversal of the prothrombotic state after abciximab treatment. We believe this is the first description of the clinical use of a near-patient test within the cardiac catheterisation laboratory to predict risk of imminent stent thrombosis.

BACKGROUND

Acute coronary thrombosis is a rare, but potentially life threatening, complication of angioplasty. It results from a prothrombotic state, which usually results from rupture of an atherosclerotic plaque or contact of blood with a foreign surface, most notably, a stent. Traditionally, treatment has been aimed at dissolving the clot with lytic therapy, but paradoxically, this itself may have prothrombotic effects.^1,2 More recently glycoprotein (Gp) IIb/IIIa inhibitors have been used. Since stent thrombosis is, fortunately, a rare complication, the routine treatment of all-comers undergoing coronary intervention with Gp IIb/IIIa inhibitor therapy to prevent stent thrombosis would be unfeasible, due to the unacceptable risk of haemorrhage and cost concerns.

Patients are routinely pre-treated with high dose dual antiplatelet medication (aspirin and clopidogrel) and anticoagulated with heparin during angioplasty, to reduce the risk of stent thrombosis. Yet, despite these measures, acute stent thrombosis continues to occur unpredictably. Some have postulated that “resistance” to antiplatelet medication may play a role.^3,4 Early identification of such a prothrombotic state could help predict imminent stent thrombosis in the catheterisation laboratory or emergency room, and help tailor antithrombotic medications in these individuals to prevent stent thrombosis.

CASE PRESENTATION

A 67-year-old man presented with anterior ST elevation myocardial infarction. On arrival he received 300 mg aspirin and clopidogrel, and was thrombolysed with a bolus of a fibrinolytic agent, reteplase, 10 U intravenously. The second bolus of reteplase was scheduled to be given half an hour later (as per dosing protocol), but the patient developed cardiogenic shock and was therefore transferred for emergency angioplasty.

Coronary angiography revealed severe stenosis with an ulcerated plaque and overlying thrombus in the proximal left anterior descending (LAD) coronary artery, and diffuse atheroma in the mid/distal vessel (fig 1). The left main stem, circumflex and right coronary arteries were unobstructed.

Figure 1.

Left coronary angiogram showing severe ulcerated left anterior descending (LAD) stenosis (arrow) with overlying hazy thrombus (external defibrillator pad visible).

TREATMENT

Heparin 5000 U was given after coronary angiography and the LAD angioplastied with a Q3.5 guiding catheter and a BMW wire. A 3.0×20 mm therapeutic perfusion balloon (ClearWay RX, Atrium Medical, USA) was used to deliver the second bolus of 10 U reteplase into the LAD at the site of the ulcerated plaque. The vessel developed severe vasospasm distally, refractory to repeated boluses of intracoronary isosorbide dinitrate, and causing severe impairment of epicardial coronary blood flow (thrombolysis in myocardial infarction (TIMI) grade I flow).

The LAD was therefore stented from distal to proximal with overlapping Cypher (Johnson & Johnson, USA) stents (from distal to proximal: 2.75×23 mm, 3.0×28 mm, 3.0×23 mm) achieving a satisfactory final result with TIMI II–III flow (fig 2).

Figure 2.

Left coronary angiogram demonstrating TIMI II–III in the LAD flow post-stenting (arrow).

Before the patient left the catheterisation laboratory, his blood was tested for thrombotic and thrombolytic status using the Global Thrombosis Test (GTT, Montrose Diagnostics, UK), a novel near-patient test which employs native (non-citrated) blood.⁵ The first phase of the test provides an assessment of physiological platelet function including aggregation and the coagulant activity of platelets (end point: occlusion time, OT). The second phase of the test is a measure of endogenous thrombolysis (lysis time, LT) and measures the spontaneous lysis of a platelet-rich thrombus.^5,6 Using a thrombus aspiration catheter (Xtract, Lumen Biomedical Inc, USA) a significant amount of thrombus was aspirated from the LAD (fig 3) and intracoronary Gp IIb/IIIa inhibitor (abciximab) was administered, resulting in a patent vessel with TIMI II-III flow (fig 4). Despite full dose reteplase, heparin, aspirin and clopidogrel, the GTT demonstrated that the patient was still markedly prothrombotic (OT 180 s, normal range 250–350 s) and endogenous thrombolysis was markedly impaired (LT >6000 s, normal range <4000 s). This was surprising given the degree of antifibrinolytic and antiplatelet medication, but highly predictive of subsequent clinical events.

Figure 3.

Thrombus aspirated from coronary artery.

Figure 4.

Final angiographic result, after thrombus aspiration and abciximab demonstrating TIMI II–III flow in the LAD.

One hour later, the patient experienced chest pain with further anterior ST elevation. Angiography revealed three focal fresh thrombi, seen as filling defects within the LAD stents (fig 5)

Figure 5.

Fresh thrombi in LAD stents, seen as filling defects (arrows).

At the end of the procedure, thrombotic and thrombolytic status was again measured. This time, the patient was no longer prothrombotic (OT 699 s); again this was predictive of subsequent clinical course. Thrombolytic status remained impaired (LT >6000 s). The patient remained well and pain-free, and made a good recovery.

DISCUSSION

We describe a case of acute coronary stent thrombosis, where an hour earlier the marked prothrombotic state was detectable using a point-of-care platelet function test (in vitro), leading to angiographically visible coronary thrombosis (in vivo), which was confirmed following aspiration of the thrombus (ex vivo).

The cause of acute stent thrombosis in our case is unclear, but likely contributors include the acute infarct setting, the relatively short time from administration of antiplatelet medication (some 3 h), the potential prothrombotic effect of the fibrinolytic therapy, and the large stent:vessel wall ratio.

We believe this is the first description of the clinical use of a near-patient test within the catheterisation laboratory to predict risk of imminent stent thrombosis. Large studies are required to investigate whether such novel point-of-care tests may allow early identification and targeted treatment of individuals at risk of such acute thrombotic events.

LEARNING POINTS

• Acute stent thrombosis is a rare but life threatening complication of angioplasty.

• The cause is unclear but there is undoubtedly a prothrombotic state.

• Early recognition and treatment with antithrombotic medication may be lifesaving.

• There is currently no reliable way to identify those at risk.

• Large studies are required to examine the potential role of point-of-care tests in identifying patients at risk of acute stent thrombosis.