Acute Vascular Occlusion Research Articles

Homozygous deletion of early growth response 1 gene and critical limb ischemia after vascular ligation in mice: Evidence for a central role in vascular homeostasis

Background The early growth response 1 gene (Egr1) encodes for an immediate to early response transcription factor that is upregulated by changes in vascular strain and hypoxia and in turn upregulates the downstream expressions of a number of angiogenic growth factors. We therefore hypothesized that early growth response 1 may be a critical early messenger governing revascularization in the setting of acute vascular occlusions. Methods C57 BL/6 mice deficient in the Egr1 gene (knockout) and their wild-type litter mates underwent ligation and excision of the femoral artery with or without the previous administration of 2.7 × 10 9 particle units of an adenoviral vector coding for the vascular endothelial growth factor gene (VEGF) or Egr1. Distal hind limb perfusion was serially measured in these animals with laser Doppler perfusion imaging. Results Wild-type mice (n = 9) had nearly complete restitution of hind limb perfusion by day 35 after ligation. In contrast, all noninjected Egr1 knockout mice (n = 5) had severe ipsilateral limb necrosis develop between 1 and 4 days after ligation ( P < .0001). Egr1 knockout mice injected with VEGF vector (n = 4) demonstrated significantly improved perfusion relative to baseline by postligation day 28, which persisted to postligation day 35 ( P < .05). Egr1 knockout animals injected with Egr1 vector (n = 7) demonstrated a partial recovery of hind limb perfusion relative to VEGF vector–treated knockout animals at postligation day 4 ( P < .01), which persisted to day 35. Conclusions These findings suggest that early growth response 1 plays a pivotal role in reperfusion responses to vascular occlusion in mice and possibly other mammals.

Lysophospholipids and their G protein-coupled receptors in biology and diseases.

Lysophospholipids and their G protein-coupled receptors in biology and diseases.

Perspectives on the role of ultrasonic devices in thrombolysis.

Reperfusion strategies in acute myocardial infarction and thrombotic vascular occlusion are focused on rapid and complete restoration of antegrade flow in the infarct-related artery in order to maximize myocardial salvage. Due to the limitations of fibrinolytic agents in restoration of vascular flow, ultrasonic clot dissolution alone and concomitantly with fibrinolytic, anti-thrombotic and echocardiographic contrast agents has been intensively studied during the last 2 decades. Ultrasound thrombolysis has been tested in-vitro and in-vivo as well as in patients with acute thrombotic occlusions. We review currently available techniques and methods of ultrasonic thrombolysis and present recent clinical and experimental data. The future role of ultrasonic thrombolysis and the strategy of "power thrombectomy" for treatment of acute coronary syndromes is also discussed.

Acute mesenteric vascular occlusion: analysis of 39 patients.

To study the factors that influence mortality and long term outcome of patients with acute mesenteric vascular occlusion. Retrospective study. University hospital, Kanazawa, Japan. Thirty-nine patients treated between 1978 and 1995 for acute mesenteric vascular occlusion. 34 patients underwent laparotomy. Bowel was resected in 29 patients, and primary anastomosis was done in 20. The occluded vessel was revascularised in 5 patients. mortality, short bowel syndrome and long term survival. 25 patients had arterial occlusions, and 8 venous. In the remaining 6, the occluded vessel was not identified. 11 Patients developed renal failure, 11 respiratory failure, and 10 disseminated intravascular coagulation (DIC). Twelve patients died within 30 days. The factors associated with early death were acidosis and high serum amylase activity. 9 Patients developed the short bowel syndrome. Survival was 49% at 1 year, and 34% at 5 years. Mortality was higher in patients with advanced peritonitis. Mesenteric revascularisation should be attempted to avoid the short bowel syndrome.

Chemokines accumulate in the lungs of rats with severe pulmonary embolism induced by polystyrene microspheres.

Pulmonary thromboembolism (PEm) is a serious and life threatening disease and the most common cause of acute pulmonary vascular occlusion. Even following successful treatment of PEm, many patients experience long-term disability due to diminished heart and lung function. Considerable damage to the lungs presumably occurs due to reperfusion injury following anti-occlusive treatments for PEm and the resulting chronic inflammatory state in the lung vasculature. We have used a rat model of irreversible PEm to ask whether pulmonary vascular occlusion in the absence of reperfusion is itself sufficient to induce an inflammatory response in lungs. By adjusting the severity of the vascular occlusion, we were able to generate hypertensive and nonhypertensive PEm, and then examine lung tissue for expression of CXC and C-C chemokine genes and bronchoalveolar lavage (BAL) fluid for the presence of chemokine proteins. Hypertensive and nonhypertensive PEm resulted in increased expression of both CXC and C-C chemokines genes in lung tissues. Hypertensive PEm was also associated with a 50-100-fold increase in protein content in lung BAL fluid, which included the CXC chemokines cytokine-induced neutrophil chemoattractant and macrophage-inflammatory protein 2. The presence of chemokines in BALs was reflected by a potent neutrophil chemotactic activity in in vitro chemotaxis assays. Abs to cytokine-induced neutrophil chemoattractant blocked the in vitro neutrophil chemotactic activity of BAL by 44%. Our results indicate that the ischemia and hypertension associated with PEm are sufficient to induce expression of proinflammatory mediators such as chemokines, and establish a proinflammatory environment in the ischemic lung even before reperfusion.

Role of platelets in the pathophysiology of acute coronary syndrome.

Coronary atherosclerosis is the primary cause of heart diseases in industrialized nations. It has now become clear that coronary atherosclerosis is not simply an inevitable consequence of aging but rather a chronic inflammatory process that can be converted into an acute clinical event by plaque rupture and arterial thrombosis. It is well recognized that platelets play a key role in thrombotic vascular occlusion at the ruptured coronary atherosclerotic plaque, leading to acute ischemic episodes, the acute coronary syndromes (ACSs). In addition, both embolization of platelet aggregates and direct, receptor-mediated platelet adhesion to the postischemic microvascular surface result in obstruction and impairment of coronary microcirculation. Such microvascular disturbance may lead to significant additional tissue injury and aggravate myocardial contractile dysfunction. Novel antiplatelet strategies have contributed substantially to improve the outcome of patients with ACSs. However, the availability of new investigative tools, including genetically modified mouse models of disease, has demonstrated that platelets not only contribute to acute thrombotic vascular occlusion but also participate in the inflammatory and matrix-degrading processes of coronary atherosclerosis itself. Platelet- endothelial cell interactions at lesion-prone sites might trigger an inflammatory response in the vessel wall early in the genesis of atherosclerosis and contribute to destabilization of advanced atherosclerotic lesions. Thus, recent progress in defining the complex multistep process that promotes firm arrest of platelets to the (sub-) endothelium and initiates subsequent platelet activation may lead to the development of new antiplatelet strategies that provide an efficacious prophylactic intervention, in particular, for patients with a high atherosclerotic risk factor profile.

Transplantation of the human uterus

Human uterine transplantation was performed on 6 April 2000 on a 26-year-old female who lost her uterus 6 years earlier due to post-partum hemorrhage. The donor, a 46-year-old patient with multiloculated ovarian cysts, underwent a hysterectomy modified to preserve tissue and vascular integrity. The donor uterus was connected in the orthotopic position to the recipient's vaginal vault and additional fixation was achieved by shortening the uterosacral ligament. The uterine arteries and veins were extended using reversed segments of the great saphenous vein, then connected to the external iliac arteries and veins, respectively. Immunosuppression was maintained by oral cyclosporine A (4 mg/kg/body wt.), azathioprine (1 mg/kg/body wt.) and prednisolone (0.2 mg/kg/body wt.). Allograft rejection was monitored by Echo–Doppler studies, magnetic resonance imaging (MRI), and measurement of the CD4/CD8 ratio in peripheral blood by fluorescence activated cell sorter (FACS scan). An episode of acute rejection was treated and controlled on the ninth day with anti-thymocytic globulin (ATG). The transplanted uterus responded well to combined estrogen–progesterone therapy, with endometrial proliferation up to 18 mm. The patient had two episodes of withdrawal bleeding upon cessation of the hormonal therapy. Unfortunately, she developed acute vascular thrombosis 99 days after transplantation, and hysterectomy was necessary. Macro- and microscopic histopathological examination revealed acute thrombosis in the vessels of the uterine body, with resulting infarction. Both fallopian tubes remained viable, however, with no evidence of rejection. The acute vascular occlusion appeared to be caused by inadequate uterine structure support, which led to probable tension, torsion, or kinking of the connected vascular uterine grafts.

Functional assessment of canine kidneys after acute vascular occlusion on Gd-DTPA-enhanced dynamic echo-planar MR imaging.

To assess the alteration in renal transit of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in dog kidneys after acute vascular occlusion on dynamic echo-planar imaging (EPI). Dynamic 240-ms EPI series (repetition time/echo time/inversion time [TR/TE/TI] = 3000/42.1/100 ms) of the midcoronal plane of both kidneys of dogs anesthetized by intravenous administration of phenobarbital sodium and ketamine hydrochloride were obtained before and after ligation of the left renal vein (n = 6) or artery (n = 6) for 40 minutes after a 2-second-rate bolus injection of a 0.05 mmol/kg dose of Gd-DTPA. Renal Gd-DTPA transit was analyzed on the time-DeltaR2* curves in each layer of the outer cortex (OC), juxtamedullary cortex and outer zone of the medulla (JMC-OM), and the inner zone of the medulla (IM). The results were compared with those in six normal animals and those of a fast gradient-echo T1-weighted dynamic study performed in other vein- (n = 6) or artery- (n = 6) occluded animals and six normal animals. The histopathological basis of the altered Gd-DTPA transit was also evaluated. The dynamic EPI showed rapid Gd-DTPA transit through each of the five concentric layers, with three separate peaks on the time-DeltaR2* curves. The vein-occluded kidneys showed immediate swelling, with a significant increase in the cross-sectional area proportion of the JMC-OM layer compared with normals (32% +/- 2% vs 24% +/- 2%, P < 0.0001) and intensely congested capillaries, tubular, obliterated material, and gradual and persistent enhancement of the OC and JMC-OM layers but poor Gd-DTPA migration to the IM layer. The artery-occluded kidneys showed a significant reduction in the entire cross-sectional area compared with normals (1352 +/- 69 vs 1432 +/- 47 mm(2), P < 0.05) and poor enhancement, with significant decreases in the area under the time-DeltaR2* curve of the OC and JMC-OM layers compared with the vein-occluded kidneys (79 +/- 50 vs 324 +/- 108 and 82 +/- 42 vs 326 +/- 113, respectively; both P < 0.0001), despite minimal histological damage. In both models, the nonaffected kidneys showed significant increases in the area under the time-DeltaR2* curves compared with baseline. The time course of vascular and tubular Gd-DTPA transit was more detailed by the EPI study than by the T1-weighted imaging study. Echo-planar imaging has an excellent ability to follow the rapid, renal Gd-DTPA transit through the regional anatomy of the canine kidney. After venous occlusion, the JMC-OM layer may be the most affected site, primarily causing renal swelling and interruption of tubular Gd-DTPA transit and concentration. In contrast, an initial block of vascular Gd-DTPA inflow is the primary effect of arterial occlusion. Nonaffected kidneys seem to compensate by increasing excretion of Gd-DTPA.

Safety and efficacy of limited-dose tissue plasminogen activator in acute vascular occlusion

Objective: The purposes of this study were to evaluate the safety and efficacy of limited-dose tissue plasminogen activator (t-PA) in patients with acute vascular occlusion and to compare these results with those obtained in equivalent patients receiving urokinase. Methods: We compared the results of 60 patients receiving catheter-directed urokinase from November 1997 to November 1998 (240,000 units/h × 4 h, 120,000 units/h thereafter for a maximum of 48 h) with those of 45 patients receiving catheter-directed t-PA from November 1998 to August 2000 (2 mg/h, total dose ≤100 mg) for acute arterial occlusion (AAO) and acute venous occlusion (AVO). Interventional approaches such as cross-catheter and coaxial techniques were used to reduce the dose of lytic agent needed to achieve pre–lysis-treatment goals (eg, complete lysis of all thrombus/unmasking graft stenosis or establishing outflow target). Statistical analysis was performed using Student t test and Fisher exact test. Results: The urokinase and t-PA groups were comparable with regard to age, comorbidities (coronary artery disease, hypertension, diabetes, renal insufficiency, smoking), duration of ischemic or occlusive symptoms, location of occlusive process, pretreatment with warfarin, and thrombotic versus embolic and native versus graft occlusion in patients with AAO. In patients with AAO and in those with AVO, t-PA was equivalent to or better than urokinase with regard to percent of clot lysis, incidence of major bleeding complications, limb salvage, and mortality. Achievement of pretreatment goals (arterial patients only) was 50% for urokinase patients and 76% for t-PA patients (P =.02). Analysis of success in individual pretreatment-goal achievement showed urokinase and t-PA to be equivalent in unmasking stenoses (85% and 84%, respectively; P = NS), whereas t-PA was superior to urokinase in the more critical task of establishing run-off (39% versus 81% for urokinase and t-PA, respectively; P =.001). Additional interventions, either endovascular or surgical, were required in 60% and 51% (P = NS) of patients receiving urokinase and t-PA, respectively, for AAO, and in 54% and 62% (P = NS) of patients receiving urokinase and t-PA, respectively, for AVO. Conclusions: Limited-dose t-PA is a safe and effective therapy for AAO and AVO when administered by experienced teams using innovative but well-established interventional techniques. (J Vasc Surg 2001;34:854-9.)

Recurrent Hypothenar Hammer Syndrome: An Unusual Presentation

Upper extremity ischemia is a relatively rare phenomenon. A case of recurrent, surgically correctable, acute digital ischemia in a worker in the maple syrup industry is presented. The present case illustrates the importance of recognizing occupational exposure to risk factors. A review of the differential diagnosis, clinical work-up and literature surrounding acute vascular occlusion of the hand and upper extremity is presented.

Free cholesterol loading of macrophages is associated with widespread mitochondrial dysfunction and activation of the mitochondrial apoptosis pathway.

Macrophage death in advanced atherosclerotic lesions leads to lesional necrosis and possibly plaque rupture and acute vascular occlusion. Among the likely causes of lesional macrophage death is intracellular accumulation of excess free cholesterol (FC), which is known to occur in vivo. We recently showed that FC loading of macrophages causes apoptosis, approximately 50% of which is mediated by activation of cell-surface FasL and triggering of the Fas pathway (Yao, P. M., and Tabas, I. (2000) J. Biol. Chem. 275, 23807-23813). To elucidate other pathways of death in FC-loaded macrophages, we investigated mitochondrial transmembrane potential (DeltaPsi(m)) and the mitochondrial apoptosis pathway in FC-loaded mouse peritoneal macrophages. Starting between 3 and 6 h of FC loading, DeltaPsi(m) was markedly decreased in the majority of macrophages and was independent of the Fas pathway. The decrease in DeltaPsi(m) by FC loading was not prevented by GSH, thus distinguishing it from 7-ketocholesterol-induced mitochondrial dysfunction. Cytochrome c release into the cytosol was noted by 4 h of FC loading, and activation of caspase-9 and effector caspases was observed at 6 h. Finally, we found that both cellular and mitochondrial levels of the pro-apoptotic protein Bax were increased severalfold as early as 4 h after FC loading. Thus, FC loading, perhaps via increased levels of Bax and/or cholesterol overloading of mitochondria, triggers cytochrome c release and activation of caspase-9 and the effector caspases, leading to macrophage apoptosis. These findings and our previous data support a model in which FC loading of macrophages promotes a dual program of caspase-mediated death.

Identification of genes potentially involved in rupture of human atherosclerotic plaques.

Although rupture of an atherosclerotic plaque is the major cause of acute vascular occlusion, the exact molecular mechanisms underlying this process are still poorly understood. In this study, we used suppression subtractive hybridization to make an inventory of genes that are differentially expressed in whole-mount human stable and ruptured plaques. Two libraries were generated, one containing 3000 clones upregulated and one containing 2000 clones downregulated in ruptured plaques. Macroarray analysis of 500 randomly chosen clones showed differential expression of 45 clones. Among the 25 clones that showed at least a 2-fold difference in expression was the gene of perilipin, upregulated in ruptured plaques, and the genes coding for fibronectin and immunoglobulin lambda chain, which were downregulated in ruptured plaques. Reverse transcriptase-polymerase chain reaction analysis on 10 individual ruptured and 10 individual stable plaques showed a striking consistency of expression for the clones SSH6, present in 8 ruptured and 2 stable plaques, and perilipin, expressed in 8 ruptured plaques and completely absent in stable plaques. Localization studies of both perilipin mRNA and protein revealed expression in cells surrounding the cholesterol clefts and in foam cells of ruptured atherosclerotic plaques. No expression was observed in nondiseased artery, and only a few cells in the shoulder region of stable plaques tested positive for perilipin. In conclusion, this study shows that it is possible to identify genes that are differentially expressed in whole-mount stable or ruptured atherosclerotic plaques. This approach may yield several potential regulators of plaque destabilization.

Effect of prolonged selective intramesenteric arterial vasodilator therapy on intestinal viability after acute segmental mesenteric vascular occlusion.

To evaluate the effect of selective intramesenteric artery vasodilator infusion on intestinal viability in a rat model of acute segmental mesenteric vascular occlusion. Although intramesenteric arterial vasodilator infusion may be an effective treatment for nonocclusive mesenteric ischemia, it has also been advocated to increase collateral blood flow after mesenteric vascular occlusion. However, the authors have previously found that intraarterial vasodilators actually reduce collateral blood flow acutely, by preferentially dilating the vasculature of adjacent, nonischemic mesenteric vascular beds, a phenomenon well established in other organs. A segment of rat ileum was acutely devascularized, with blood flow provided only by collateral arterial vessels from adjacent, nonischemic bowel. Papaverine (30 or 40 microg/kg/min), isoproterenol (0.06 microg/kg/min), norepinephrine (0.1 or 0.2 microg/kg/min), or vehicle saline was continuously infused into the cranial (superior) mesenteric artery for 48 hours. Viability was then assessed using previously established, objective gross and microscopic criteria. Although papaverine increased total mesenteric blood flow in normally vascularized rats, it not only failed to improve but actually significantly reduced the length of the devascularized segment maintained viable by collateral blood flow after 48 hours. Isoproterenol had a similar effect. Norepinephrine infusion decreased both normal mesenteric blood flow and viable segment length. These findings suggest that intraarterial vasodilator therapy fails to improve intestinal viability after segmental mesenteric vascular occlusion.

Niedrigdosierte Thrombolyse mit rt-PA bei langstreckigen peripheren arteriellen Verschlüssen

To evaluate the efficacy of intra-arterial thrombolysis by rt-PA in acute and subacute extensive peripheral vascular occlusion. 100 patients with acute and subacute occlusion of peripheral arteries were treated by catheter thrombolysis using 20 mg of rt-PA over a period of 20-24 hours. In all cases the occlusion extended to more than 20 cm and two stages of the extremity were involved. In 80 patients the original vessels (69/80 by thrombosis, 11/80 by embolization) and in 20 cases the femoro-popliteal bypass vessel was occluded. A catheter was inserted into the thrombus into which rt-PA and heparin were separately infused by two injectors. Heparin was given in a dose of 800-1000 U/h depending on the continuously monitored PTT levels. A control angiography was performed after 10 mg of rt-PA. After successful thrombolysis either PTA or aspiration thrombectomy was performed, if necessary, to reestablish a nearly normal vascular lumen. Open arteries of the thigh and at least one main vessel of lower leg was considered as success. Recanalization of the original vessels was successfully by thrombolysis, PTA or aspiration thrombectomy in 68/80 [85%] cases. Thrombolysis and PTA reestablished a normal lumen of the bypass vessel in 11/20 [65%] and in 6 more cases a recanalization with minor stenosis. In 13/15 patients with critical ischemia, thrombolysis probably helped to avoid amputation by reopening smaller collateral arteries. Bleeding at the puncture site, as a complication of thrombolysis, was the reason for stopping therapy in three cases. There was no retroperitoneal or cerebral bleeding. After successful thrombolysis, reocclusion occurred in 15 patients within one year, only in five cases amputation was necessary. Extensive occlusion of peripheral arteries or of a femoro-cural bypass can be successfully treated by low dose rt-PA thrombolysis with a low complication rate. Even partial reopening may prevent amputation.

Mesenteric vascular occlusion resulting in intestinal necrosis in children

Purpose: The records of 4 patients who had necrotic bowel secondary to acute mesenteric vascular occlusion affecting various levels of mesenteric vasculature were reviewed to determine the clinical manifestations, diagnostic investigations, predisposing factors, complications, and outcome of mesenteric vascular thrombosis in children. Methods: The medical records of the patients (3 boys, 1 girl) treated between 1981 and 1996, inclusive, for bowel infarction secondary to mesenteric vascular thrombosis, were reviewed with regard to signs and symptoms, laboratory tests, radiological investigations, surgical findings, histopathologic examinations, and outcome. Results: The ages of the patients ranged between 1 and 14 years with a mean age of 8.2 years. Initial symptoms, present in all patients, were abdominal pain, abdominal distension, and tenderness. Laboratory and radiological findings including abdominal radiographs and abdominal ultrasonography were nondiagnostic. Selective superior mesenteric angiography showed complete obliteration of the superior mesenteric artery with absence of venous return in 1 case. Three patients with massive intestinal necrosis died of multiorgan failure or the complications of short bowel syndrome. Histological examination of the resected intestinal segments showed the typical findings of polyarteritis nodosa in 2 patients. One patient had a previous history of right femoral vein thrombosis, whereas 1 patient had no known underlying disorders predisposing vascular thrombosis. Conclusions: Mesenteric vascular occlusion is a rare but serious disease leading to death in children. The patients present with similar clinical signs, most frequent and important are acute abdominal pain, vomiting, and distension. Mesenteric vascular occlusion is a rare cause of acute abdomen in childhood, which requires urgent diagnosis and intervention. In suspected mesenteric vascular insufficiency, angiography should be performed followed by intraarterial thrombolytic infusion therapy in selected cases. When intestinal infarction is suspected, immediate surgical resection of compromised bowel is necessary with appropriate postoperative anticoagulation or treatment of any underlying disease. J Pediatr Surg 35:1161-1164. Copyright © 2000 by W.B. Saunders Company.

Acute carotid occlusion alters the activation flow coupling response to forepaw stimulation in a rat model.

To determine whether the hemodynamic response to functional stimulation is sensitive to proximal arterial occlusion, we measured the activation flow coupling response in a rat model of acute reversible vascular occlusion. In alpha-chloralose-anesthetized rats (n=18), laser Doppler measurements were made through a thinned skull over the somatosensory cortex in response to electrical forepaw stimulation. Signal-averaged responses to 4 and 8 seconds of electrical forepaw stimulation were obtained before, during, and shortly after acute unilateral or bilateral carotid occlusion produced with the use of a surgically placed snare. Baseline cerebral blood flow was significantly decreased over the forepaw region of the somatosensory cortex after both occlusion of the carotid contralateral to the stimulated forepaw and bilateral occlusion compared with preocclusion (P<0.05). Postocclusion and ipsilateral occlusion led to a nonsignificant increase in baseline cerebral blood flow compared with preocclusion. Contralateral carotid occlusion and bilateral occlusion significantly prolonged the temporal characteristics of the flow response, especially the delay to peak (P<0.05), compared with preocclusion, whereas ipsilateral carotid occlusion significantly shortened the delay to peak (P<0.05). Only contralateral carotid occlusion produced a significant reduction in the peak amplitude of the flow response compared with preocclusion (P<0.05). These findings suggest that temporal characteristics of functional activation responses are sensitive to alterations in the proximal arterial supply and, conversely, that functional activation studies must be interpreted with consideration of proximal arterial disease.

Role of WHO-MONICA Project in unravelling of the cardiovascular puzzle

Understanding of cardiovascular disease has grown exponentially over the past few decades because of an intensive multidisciplinary research effort. Bench research has clarified the pathophysiology of atherosclerosis and acute vascular occlusion. Epidemiological research has identified the importance of specific independent risk factors and improved the degree to which people at increased risk of the disease can be identified. And clinical trials have conclusively shown which treatments work and which ones fall short of expectations.

Peripheral arterial occlusion in acute promyelocytic leukemia

A 16-year-old Caucasian teenager developed fatigue, abdominal pain, pneumonia, and subsequently acute vascular occlusion of the left superficial femoral artery. Vascular assessment and heparin therapy lead to bone marrow aspiration and a diagnosis of acute promyelocytic leukemia. Treatment with chemotherapy prevented loss of limb and avoided further vascular surgery. Young patients with acute vascular occlusion require an in-depth assessment including attention to hematological disorders. Clots obtained on thromboembolectomy should be sent for pathological assessment and not discarded, especially in an unusual-age patient for arterial embolus.

Peripheral Arterial Occlusion in Acute Promyelocytic Leukemia

A 16-year-old Caucasian teenager developed fatigue, abdominal pain, pneumonia, and subsequently acute vascular occlusion of the left superficial femoral artery. Vascular assessment and heparin therapy lead to bone marrow aspiration and a diagnosis of acute promyelocytic leukemia. Treatment with chemotherapy prevented loss of limb and avoided further vascular surgery. Young patients with acute vascular occlusion require an in-depth assessment including attention to hematological disorders. Clots obtained on thromboembolectomy should be sent for pathological assessment and not discarded, especially in an unusual-age patient for arterial embolus.

A role for changes in platelet production in the cause of acute coronary syndromes.

Platelets are heterogeneous with respect to their size, density, and reactivity. Large platelets are more active hemostatically, and platelet volume has been found to be increased both in patients with unstable angina and with myocardial infarction. Furthermore, platelet volume is a predictor of a further ischemic event and death when measured after myocardial infarction. Platelets which are anucleate cells with no DNA are derived from their precursor, the megakaryocyte. Therefore, it is suggested that changes in platelet size are determined at thrombopoiesis in the megakaryocyte and that those changes might precede acute cardiac events. Understanding of the signaling system that controls platelet production may also further elucidate the cascade of events leading to acute vascular occlusion in some patients.