Donald Silver

Heparin-induced thrombocytopenia in the newborn

This pilot study was initiated to determine whether heparin-induced thrombocytopenia occurs in the newborn and whether thromboembolic complications in the newborn could be related to heparin-induced thrombocytopenia. Thirty-four infants in whom thrombocytopenia (less than 70,000/mm3) (n = 23), precipitous (30% to 50%) fall in platelet count (n = 5), or thromboses (n = 6) developed while they were receiving heparin were studied. Heparin-associated antiplatelet antibodies were demonstrated in 14 infants by platelet aggregation testing. The average gestational age (29 +/- 6 weeks); birth weight (1300 +/- 945 gm); and platelet count at birth (234,000/mm3 +/- 111,000/mm3) of these 14 infants did not differ statistically from the 20 infants without heparin-associated antiplatelet antibodies. An umbilical artery catheter was inserted in all infants except a single patient from each group. Aortic thrombosis was documented by abdominal ultrasonography in 11 of 13 (85%) infants with heparin-associated antiplatelet antibodies. One patient died with a midgut volvulus before the aorta could be examined. Five aortic thromboses were detected in the 20 infants without heparin-associated antiplatelet antibodies. Bleeding was not associated with the heparin-induced thrombocytopenia. One patient with previously demonstrated thrombocytopenia and heparin-associated antiplatelet antibodies had recurrent thrombocytopenia when reexposed to heparin; her platelet count recovered after heparin withdrawal. Thus heparin-induced thrombocytopenia does occur in preterm and term infants receiving heparin and is associated with arterial thromboses. Therefore infants receiving any form or amount of heparin must be carefully monitored for heparin-induced thrombocytopenia.1+

Heparin-coated catheters and heparin-induced thrombocytopenia.

Ten patients with heparin-coated pulmonary artery catheters had heparin-induced thrombocytopenia, which persisted after all other sources of heparin were discontinued. The thrombocytopenia occurred in approximately 0.4% of the patients receiving heparin-coated catheters and remitted when the catheters were removed. The platelet counts averaged 59,000/mm3 at the time of the diagnosis and recovered to an average of 143,000/mm3 by 3 days (range 2 to 4 days) after removal of the heparin-coated catheters. One patient required a second catheter 31 days after the first catheter had been removed. When the second heparin-coated catheter was inserted, the platelet count decreased from 307,000/mm3 to 102,000/mm3 in 4 days. Segments of heparin-coated pulmonary artery catheters were placed in platelet-rich plasma and incubated with serum from patients with known heparin-associated antiplatelet antibodies or with serum from volunteers with no exposure to heparin. The heparin-coated catheters induced platelet aggregation in all samples containing serum from patients with heparin-induced thrombocytopenia. However, platelet aggregation did not occur when the catheters were incubated with the serum of the volunteers. Non-heparin-coated catheters failed to produce platelet aggregation when incubated with either sera. The high mortality and morbidity rates associated with heparin-induced thrombocytopenia mandate that afflicted patients receive no more heparin, at least until the heparin-associated antiplatelet antibodies are no longer detectable. Patients with heparin-coated catheters who have thrombocytopenia should be tested for the presence of heparin-associated antiplatelet antibodies. If heparin-induced thrombocytopenia is confirmed, the catheters must be removed if the thrombocytopenia is to be reversed and complication avoided.

Heparin-induced thrombocytopenia in open heart surgical patients: Sequelae of late recognition

Most patients undergoing open heart operations have had exposure to heparin for diagnostic and/or therapeutic procedures. Heparin antibody formation and heparin-induced thrombocytopenia with repeat heparin administration can cause high morbidity and mortality from thrombotic complications, especially when delay in diagnosis occurs. From 1981 to 1991, heparin-induced thrombocytopenia was diagnosed in 82 of 4,261 open heart surgical patients (1.9%). Platelet counts less than 100 x 10(9)/L (100,000/microL) or new or recurring thrombotic events prompted suspicion of heparin-induced thrombocytopenia. Heparin-dependent antibody was diagnosed preoperatively in 12 patients (group I) and postoperatively in 70 patients (group II). Heparin was not given postoperatively in group I patients, and complications in this group were limited to bleeding in 3 patients. There were no thromboembolic events and all patients survived. Group II patients had late recognition of heparin-dependent antibody postoperatively, and heparin exposure was continued for varying periods postoperatively. Thirty-seven group II patients (53%) had bleeding complications and 31 (44%) had thromboembolic complications. These complications led to death in 23 group II patients (33%). Heparin-dependent antibody may occur in patients having open heart operations and is a major cause of morbidity and mortality if not diagnosed early with cessation of heparin therapy.

Aneurysms and pseudoaneurysms of the superficial temporal artery caused by trauma

Superficial temporal artery (STA) aneurysms as a result of trauma represent less than 1% of reported aneurysms. During the past 200 years only the type of trauma and the preferred treatment have significantly changed. Patients are generally young men with a recent history of blunt head trauma. They may complain of a mass, headache, or other vague symptoms. Neurologic defects are rare; however, if a neurologic deficit exists, the physician should consider either arteriography or a head CT scan to search for intracranial pathologic conditions. In most cases the diagnosis may be made by obtaining a complete history and physical examination. The treatment of choice is ligation and resection, which may be accomplished with the patient under local or general anesthesia. In rare instances, arteriography with selective embolization may be useful when the traumatic aneurysm is complicated by severe facial trauma. Three cases of STA aneurysms are presented. The history, pathophysiology, origin, presentation, diagnosis, differential diagnosis, and treatment of STA aneurysms are reviewed.

Surgical management of refractory venous stasis ulceration

A 15-year experience with 27 patients, 20 to 75 years of age, with refractory venous stasis ulcers is presented. All patients had been managed with support hose, elevation, elastic wraps, Unnas paste boots, and graduated compression stockings. Because of multiple recurrences of their ulcers, the patients were offered surgical treatment to reduce the venous hypertension in the areas of ulceration. The 27 patients had 32 modified Linton procedures. Five had bilateral procedures. At the time of operation, 18 limbs had medial malleolar ulcers, five had bimalleolar ulcers, four had lateral ulcers, three had posterior ulcers, and two patients were free of ulcer. Medial incisions were used in 20 limbs, lateral incisions in six, medial and lateral incisions in three, and midposterior incisions in three. Split-thickness skin grafts were placed on six limbs the day of surgery and on 22 limbs 4 to 7 days later. Postoperative complications included deep venous thrombosis in two, partial flap necrosis in three, and cellulitis of the lower leg in three patients. Follow-up has ranged from 6 months to 10 years. During the most recent clinic visits, 21 limbs were completely healed, whereas six limbs had a recurrence of the ulcer. Five patients have been lost to follow-up. The good long-term results in 78% of the cases indicate that patients with recurrent venous stasis ulcers may receive lasting benefit from modified Linton procedures.

Effect of pentoxifylline on tissue injury and platelet-activating factor production during ischemia-reperfusion injury*

PURPOSE Pentoxifylline lessens the metabolic derangements associated with ischemia-reperfusion injury. This study evaluated the effects of pentoxifylline on platelet-activating factor (PAF) production and tissue injury during skeletal muscle ischemia-reperfusion injury. METHODS The isolated canine gracilis muscle model was used. Group 1 muscles were subjected to 5 hours of ischemia and 20 hours of reperfusion (n = 10); group 2 muscles received pentoxifylline, 15 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6); group 3 muscles received pentoxifylline, 25 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6). PAF was measured from muscle venous effluent by the scintillation proximity assay method. Muscle injury was assessed by vital staining and planimetry. RESULTS PAF levels in group 2 were decreased at 10, 15, and 30 minutes of reperfusion compared with group 1 but did not reach significance. PAF levels in group 3 were decreased at all times of reperfusion compared with group 1 but attained significance only at 10 minutes of reperfusion (p < 0.05). No significant differences in muscle weight were noted among the three groups. No differences in the extent of muscle necrosis was observed between group 1 (77.26% +/- 20.38%) and group 2 (60.49% +/- 23.97%) (p = 0.08); there was a significant reduction in the extent of muscle necrosis in group 3 (44.55% +/- 21.47%) compared with group 1 (p < 0.05). CONCLUSIONS The administration of pentoxifylline at 25 mg/kg before reperfusion of ischemic skeletal muscle decreased significantly the extent of muscle necrosis and PAF levels in the venous effluents at all times of reperfusion (significantly at 10 minutes). These results suggest that pentoxifylline may decrease tissue injury of ischemia-reperfusion by inhibiting the production of PAF during critical periods of reperfusion.

Reexposure to heparin of patients with heparin-associated antibodies.

Four patients with heparin-associated antiplatelet antibodies who were not receiving platelet function-inhibiting agents received heparin during surgery, angiography, or hemodialysis. Three of the four patients had complications that were attributed to heparin-induced platelet aggregation. The complications included a superficial femoral artery thrombosis, a thrombotic stroke after a carotid endarterectomy, and recurring thrombosis of a graft inserted for dialysis. Nine patients received aspirin (325 mg b.i.d.) or dipyridamole (Persantine) (200 to 300 mg daily) before reexposure to 5000 to 12,000 units of heparin during 11 vascular procedures. The procedures included two carotid endarterectomies, three aortofemoral bypasses, one femoropopliteal bypass, two femorotibial in situ saphenous vein bypasses, one iliofemoral thrombectomy, one bilateral iliac artery angioplasty, and one axillobifemoral bypass. Platelet counts averaged 173,000/mm3 before heparin reexposure, fell to an average of 86,000/mm3 within 24 hours of heparin reexposure, and returned to normal within 48 hours after the reexposure. None of these patients had a thromboembolic or hemorrhagic complication. Patients with heparin-associated antiplatelet antibodies are at risk for developing thrombocytopenia and thromboembolic complications on reexposure to heparin. The platelet function-inhibiting agents, aspirin and Persantine, protect the patients from the thromboembolic complications but not the thrombocytopenia associated with limited heparin reexposure.

The role of heparin-associated antiplatelet antibodies in the outcome of arterial reconstruction.

PURPOSE This study was designed to determine the incidence rate of heparin-associated antiplatelet antibodies (HAAb) in patients who require major vascular reconstruction and to determine whether the HAAb were associated with perioperative thrombotic events. METHODS One hundred six patients who underwent elective arterial reconstruction for cerebrovascular occlusive disease (n = 48), aortoiliac occlusive disease (n = 13), aortoiliac aneurysm (n = 17), mesenteric arterial occlusive disease (n = 1), or infrainguinal arterial occlusive disease (n = 28) prospectively underwent evaluation from July 1, 1996, to June 30, 1997. Heparin-associated antibody tests (with a two-point platelet aggregation assay) and platelet counts (via Coulter counter) were performed before surgery and on or after the 4th day after vascular reconstruction. Arterial reconstruction thromboses were established by means of duplex ultrasound scanning or angiography. Acute myocardial infarction (AMI) and venous thromboses were diagnosed with clinical criteria and duplex ultrasound scanning, respectively. A significant decrease in platelet count was defined as a platelet count of less than 100, 000/mm3 or as a more than 30% drop in the platelet count. RESULTS Twenty-two patients (21%) had at least one positive HAAb assay: one assay was positive before surgery only (after angiography), six were positive both before and after surgery, and 15 were positive after surgery only. There were three perioperative deaths-one in the HAAb-positive group and two in the HAAb-negative group. Ten thrombotic events occurred in the perioperative period. Four thrombotic events (three operative site thromboses and one AMI) occurred in the HAAb-positive group (18.2%). All of these patients were undergoing heparin therapy. Of the six patients (with three operative site thromboses, two deep venous thromboses, and one AMI) in the HAAb-negative group (7%; P =.21), three were undergoing heparin therapy. No patient who was HAAb positive with a thrombotic event had thrombocytopenia or a significant decrease in platelet count. CONCLUSION The frequent exposure to heparin by patients with peripheral vascular disease is associated with a high incidence rate (21%) of HAAb formation, which makes it one of the more common hypercoagulable conditions in these patients. The patients who were HAAb positive had a 2.6-fold increase in perioperative thrombotic events. Thrombocytopenia or decreasing platelet counts were not reliable clinical markers for identifying patients who were HAAb positive. It is suggested that all patients who have undergone heparin therapy and who have an unexplained perioperative thrombotic event develop should undergo testing for HAAb.

Use of enoxaparin in patients with heparin-induced thrombocytopenia syndrome

PURPOSE To determine whether low molecular weight heparin (LMWH) can be an alternative to unfractionated heparin (UH) for patients with heparin-induced thrombocytopenia syndrome (HIT). METHODS The diagnosis of HIT was established in 126 patients by platelet aggregometry with UH (1 U/ml). These plasma samples were also tested for the ability to aggregate platelets in the presence of the LMWH enoxaparin (1 U/ml). Two patients with the HIT syndrome, after negative platelet aggregometry testing with enoxaparin, were anticoagulated with enoxaparin. RESULTS Fifteen plasma samples that tested negative to UH also tested negative to enoxaparin. Forty-three of 126 (34%) UH-positive plasma samples aggregated platelets in the presence of enoxaparin. Twenty-two of 102 (22%) plasma samples with limited positive aggregation responses (minimal or no change in optical density) aggregated platelets in the presence of enoxaparin. However, 21 of 24 (88%) strongly positive plasma samples (30% to 60% change in optical density at 3 to 27 minutes) also aggregated platelets in the presence of enoxaparin. Two patients with HIT who received enoxaparin after aggregation testing demonstrated no cross-reactivity to enoxaparin achieved adequate anticoagulation and did not develop HIT. CONCLUSIONS Thirty-four percent of plasma samples from patients with HIT (88% of those strongly positive) aggregated platelets in the presence of enoxaparin. Patients with HIT may safely receive enoxaparin if their plasma does not aggregate platelets in the presence of enoxaparin.

Rural Vascular Trauma: A Twenty-Year Review

A 20-year review documented 248 vascular injuries in 210 patients from principally rural areas. The average time between injury and treatment from 1970 to 1983 was 6 hours. Between 1983 to 1990, when 46% of patients were transported by helicopter, the average delay was 4 hours. Blunt trauma (41%, with 29% motor vehicle accidents and 12% farm/industrial accidents) caused the most severe injuries and accounted for most amputations (89%) and deaths (80%). All of the blunt trauma patients had associated injuries. Penetrating injuries occurred in 59% of the patients and accounted for 11 % of the amputations and 20% of the deaths. Extremity vessels were injured 73% of the time (upper extremity, 47%; lower extremity, 26%). Eightyseven percent of the vessels injured were arteries and 13% were major venous injuries. Preoperative arteriograms were obtained in 30% of our patients. Vascular injury was determined in the others at the time of operative exploration. Vascular repair included direct anastomosis or lateral suture repair (51%), autogenous vein graft (16%), synthetic graft (6%), and ligation (19%). Primary amputation and thrombectomy were other (8%) initial treatments. In the past 10 years concomitant major peripheral venous injuries were repaired in six patients (one amputation) and ligated in one patient (no amputation). The mortality rates (4.8% total) for patients with blunt and penetrating trauma were 9.3% and 1.6%, respectively. Survival rates have not improved since the implementation of a helicopter transport system in 1983, but the amputation rate declined from 18% to 7%.