Roque Pifarré

Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia.

PURPOSEnThe complications of heparin-induced thrombocytopenia include thrombosis and death. The purpose of the study was to determine whether early heparin cessation can prevent these outcomes.nnnSUBJECTS AND METHODSnWe performed a retrospective analysis of consecutive patients with heparin-induced thrombocytopenia diagnosed by platelet aggregometry. Demographic, clinical, and laboratory findings were compared in patients by whether heparin treatment was stopped early (< or = 48 hours) or late (>48 hours) after the onset of thrombocytopenia, as well as between patients with and without thrombosis. Thrombocytopenia was defined as a 50% decline in baseline platelet counts or an absolute platelet count < 100,000/mm3.nnnRESULTSnOf the 113 patients, 38% developed thrombosis and 27% died. One-half of patients had thrombosis diagnosed >24 hours after heparin cessation. No difference in thrombosis or mortality was found in the 40 patients with early heparin cessation [mean (+/-SD) time of cessation 0.7 +/- 0.6 days] compared with the 73 patients with late heparin cessation (5 +/- 3 days). Thrombosis >24 hours after heparin cessation occurred in 61% of the patients in the early group and in 40% of the late group (P = 0.17). In a multivariate analysis, only a lower nadir of the platelet count (percent of baseline) was associated with thrombosis. Neither thrombosis nor the time to heparin cessation were associated with mortality.nnnCONCLUSIONSnEarly heparin cessation was not effective in reducing morbid events in patients with heparin-induced thrombocytopenia. Treatment strategies other than heparin cessation alone should be considered in patients with this condition.

New anticoagulants for the cardiovascular patient

Manuscript received May 9, 1994; accepted July 7, 1994. Address correspondence and reprint requests to Dr. Jeanine M. Walenga, Department of Pathology, Loyola University Med ical Center, 2160 South First Avenue, Maywood, IL 60153, U.S.A. Summary: Invasive cardiac procedures and cardiac sur gery, which have become a significant component of health care, provide a particular case scenario where there are special considerations given to control bleeding and to have available alternative anticoagulants for pa tients unable to tolerate heparin (e.g., heparin-induced thrombocytopenia). We describe a comprehensive proto col for blood preservation in cardiac surgery incorporat ing the patients medical history, autologous transfusions, and intraoperative techniques of heparin and protamine titration and dosing. Furthermore, various new anticoag ulants under clinical development are discussed, particu larly hirudin, hirulog, iloprost, ancrod, Lomoparan, low- molecular-weight heparins, 1-deamino-8-D-arginine- vasopressin (DDAVP), and aprotinin. These approaches should benefit the patient with difficult to control periop erative bleeding, heparin-induced thrombocytopenia, al lergic reactions to protamine, platelet dysfunction, and poor response to heparin (e.g., due to antithrombin III deficiency).

Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina.

Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of an inelastic aortic synthetic vascular graft on exercise hemodynamics

This study compared aortic input impedance characteristics between patients with aortic interposition Dacron grafts placed for traumatic aortic injury and normal age-matched control subjects. All subjects were examined at rest and after treadmill exercise. Magnetic resonance imaging was conducted to rule out anatomic (stenosis) effects. Exercise increased characteristic impedance (ie, reduced aortic distensibility) by 29% and decreased total systemic arterial compliance by 21% in the patient group, whereas the normal control group showed insignificant change in these variables after exercise. Peripheral pressure wave reflection was reduced substantially with exercise (27%) in the control group, with much less reduction observed in the patient group. These abnormal vascular hemodynamics were associated with significantly high cardiac energetic costs in the patient group. A plausible explanation for the observed differences lies in the exaggerated vascular impedance mismatch between compliant aorta and inelastic graft, when cardiac output increases dramatically.

POTENTIAL USE OF RECOMBINANT HIRUDIN AS AN ANTICOAGULANT IN A CARDIOPULMONARY BYPASS MODEL

Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass operations. Two administration regimens were used for r-hirudin: group 1, 1.0 mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group 2, 1.0 mg/kg intracardiac bolus with 1.25 +/- 0.04 mg.kg-1.h-1 intravenous infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (p = 0.02). Decreases in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the same in each group. The bleeding time assay showed less prolongation for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life all coagulation variables returned to baseline within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in cardiopulmonary bypass. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Ventricular aneurysm due to blunt chest injury

A left ventricular aneurysm developed in 3 patients sustaining blunt chest injury. Evidence of an acute myocardial infarction on the electrocardiogram and enzyme analysis prompted cardiac catheterization, which revealed total occlusion of the left anterior descending coronary artery in 2 of the 3 patients. Ventricular aneurysmectomy was performed in each patient. A review of the literature revealed 32 previously reported patients with left ventricular aneurysm caused by blunt trauma. Clinical features, catheterization or autopsy findings, and outcome are examined.

Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass operations

BACKGROUNDnAprotinin significantly decreases postoperative blood loss, yet its exact mechanism of action remains unproven.nnnMETHODSnTo study the cytoprotective effect on platelets, we collected blood samples from patients during cardiopulmonary bypass (CPB) operations performed with or without aprotinin. Analysis included whole-blood flow cytometry.nnnRESULTSnThe highest percentages of activated platelets (positive for GMP-140 expression) were bound to leukocytes and erythrocytes in all CPB patients. Platelet-platelet activation did not reveal any marked differences between groups. However, in the platelet-cell bound region, increased ristocetin-stimulated platelet activation was observed from 30 minutes on CPB to 90 minutes after CPB with aprotinin (11.9% +/- 5.1% to 33.1% +/- 8.6%; p < 0.05), but not without aprotinin (17.5% +/- 0.1% to 17.9% +/- 2.3%). Platelet autoactivation increased more in the untreated group with time on CPB.nnnCONCLUSIONSnThis study demonstrates that in the presence of aprotinin, platelets remain unstimulated during CPB and the von Willebrand GPIb-mediated activatability of platelets is preserved, thus maintaining a viable platelet population. Most important, this study reveals that these mechanisms are more related to platelet-leukocyte than to platelet-platelet interactions.

DIAGNOSIS OF DISSECTING AORTIC ANEURYSM BY COMPUTED TOMOGRAPHY

Computed tomography (CT) of the torso combined with simultaneous intravenous bolus injection of contrast media was used in sixteen patients suspected of having dissected their aorta. All patients had subsequent correlative percutaneous aortography within 24 h of the CT examination. Four patients proved to be normal, one had an aneurysm of the thoracic aorta, and eleven had aortic dissection (five type I, six type III dissection). All eleven patients with aortic dissections were diagnosed by CT and angiography; nine had spontaneous dissections and two had iatrogenic injuries to the aorta. Limitations of this imaging procedure include; inability to detect aortic valvular dysfunction and failure to provide an adequate perspective of aortic branch involvement. Potential benefits include: avoidance of aortogram in some cases, relative non-invasiveness, rapidity and ease of procedure, and less expense, radiation, contrast media, and discomfort to the patient. Early experience with CT-enhancement technique has reliably demonstrated normal as well as abnormal aortic wall morphology. It may have a place as an alternative to the conventional aortogram.

Effects of aprotinin on anticoagulant monitoring implications in cardiovascular surgery

This study was designed to evaluate anticoagulant monitoring of heparin and platelet function in the presence of aprotinin. Aprotinin added to heparinized whole blood at concentrations equal to (30 micrograms/mL), twice, and four times that used in cardiopulmonary bypass operations synergistically elevated the activated clotting time (ACT) (536 +/- 73, 651 +/- 86, and 787 +/- 71 seconds, respectively) over the value with heparin alone (384 +/- 66 seconds) (p < 0.001). In addition, the ACT of heparin-aprotinin mixtures supplemented with protamine showed that the heparin was not completely neutralized (131 +/- 12 versus 98 +/- 7 seconds). Specific tests revealed that the effect on ACT caused by aprotinin is not equal to the anticoagulant effect of heparin. Thus there is a risk of under-heparinization if the ACT is used as a monitor when aprotinin is present. Furthermore, protamine doses relative to the heparin concentration, and not relative to the ACT, should be used to reverse heparin. In studying the effects of aprotinin on platelet function, there was a significant inhibition of aggregation when normal platelets were supplemented with aprotinin, but not for platelets of postoperative patients. This suggests that aprotinin may interact more favorably with nonactivated platelet surfaces, reducing or inhibiting the expression of receptors. Thus it is necessary to treat a patient with aprotinin before beginning cardiopulmonary bypass. Based on these data, the effect of aprotinin on the hemostatic system and its drug interactions must be considered to optimize safety and efficacy during cardiopulmonary bypass operations.

Safety of patent ductus arteriosus closure in premature infants without tube thoracostomy

During a 30-month period, 34 premature infants underwent surgical closure of a patent ductus arteriosus. The mean gestational age at birth was 25 +/- 0.3 weeks and the mean age at the time of operation was 3 +/- 0.3 weeks (mean weight, 829 +/- 54 g). Indomethacin therapy had failed in 32 patients, and 2 had contraindications to its use. The initial 8 patients had parascapular incision and ligation of the patent ductus arteriosus; the last 26 patients had a short transaxillary incision and clipping. The average duration of the operation from the time of incision to skin closure was 36 +/- 2 minutes (range, 15 to 65 minutes). One patient (3%) needed chest tube insertion intraoperatively because of visceral pleura disruption. Two patients (5.8%) had a small pneumothorax (< 10% of the lung field) that resolved within 24 hours. There was no morbidity or mortality directly related to the operative procedure, although 3 patients (8.8%) ultimately died from problems related to their severe prematurity. We conclude that surgical closure of patent ductus arteriosus without chest tube drainage can be accomplished safely in premature infants. Postoperative nursing care is simplified and the cost is reduced because the need for the chest tube and drainage system is eliminated and the number of chest radiograms needed postoperatively is reduced.