Heparin-induced thrombopenia: rapid regression of thrombopenia and thrombosis after plasma exchange. Case report

INTRODUCTION: Heparin-induced thrombocytopenia with thrombosis is a rare but severe adverse reaction to heparin therapy, whose management is difficult. After heparin withdrawal, the initiation of an alternative anticoagulant therapy, such as recombinant hirudin or danaparoid, is strongly recommended before vitamin K antagonists are effective. Several reports of the efficacity of plasma exchanges in patients with life-threatening thrombosis have been made. EXEGESIS: We report on a patient with severe aortic thrombosis related to heparin therapy in whom a unique plasma exchange resulted in both dramatic improvement in the platelet count and marked reduction of the thrombosis. CONCLUSION: This case provides further evidence that plasma exchanges can be useful in the management of heparin-induced thrombocytopenia with thrombosis. They are rapidly efficient and can be used before heparin alternative treatment is effective.     

Budd-Chiari syndrome: a common complication of Beh?et's disease

OBJECTIVE: The Budd-Chiari syndrome is characterized by venous outflow obstruction of the liver, usually occurring as a consequence of thrombosis of the hepatic veins. Vasculitis is a major component of Beh?et's syndrome. The aim of this study was to determine the incidence of hepatic vein thrombosis in patients with Beh?et's disease and to estimate the effect of this entity upon the clinical features and course of Beh?et's syndrome. METHODS: During an 8-yr period from 1985 to 1994, from a total of 493 patients with Beh?et's disease seen at Hacettepe University Hospital, the incidence and effect of hepatic vein thrombosis on the clinical course of Beh?et's syndrome was investigated. The hepatic vein thrombosis in each case was documented by hepatic venography and confirmed by digital subtraction angiography, computed tomography, ultrasonography, and liver biopsy. Coagulation parameters including protein C, protein S, and anti-thrombin III levels were easured in each case. The survival of cases with Beh?et's syndrome complicated by Budd-Chiari syndrome and the effect of the Budd-Chiari syndrome on the survival of individuals with Beh?et's syndrome were determined using the Kaplan-Meier technique. RESULTS: Of the 493 cases of Beh?et's syndrome, 53 (10.8%) were found to have one or more large vessel thrombosis. Of these 53 patients, 14 (26.4%) had hepatic vein thrombosis. Of these 14 patients, 8 had an additional inferior vena cava thrombosis and 4 had portal vein as well as total inferior vena cava thrombosis. Only two patients with isolated hepatic vein thrombosis were identified. These two patients and two additional patients with hepatic vein thrombosis plus thrombosis of the hepatic portion of the inferior vena cava are currently alive. Of the 10 patients with total inferior vena cava and hepatic vein thrombosis (4 also had portal vein thrombosis), all 10 died with a mean survival of 10.3 months. During the same time period, 37 patients obtained from a total of 1494 patients with clinical evidence of either portal hypertension, hepatic venous outflow obstruction or inferior vena caval obstruction without Beh?et's syndrome were found to have a Budd-Chiari syndrome. Of these 37 patients, 19 (51%) had an identifiable underlying disorder responsible for their hepatic vein thrombosis. CONCLUSION: Based upon this experience, it appears as if Budd-Chiari syndrome is a relatively frequent complication of Beh?et's disease. When individuals with Beh?et's syndrome have BCS, concurrent thrombosis of the portal vein and inferior vena cava are often found, if the patency of these vessels is assessed. The clinical course of patients with Beh?et's syndrome complicated by Budd-Chiari syndrome is poor. The extent of the vascular thrombosis within the inferior vena cava rather than the presence of the hepatic vein thrombosis per se is the major determinant of survival.     

Refractory ascites due to portal vein thrombosis in liver cirrhosis--report of two cases

Portal vein thrombosis as a complication of liver cirrhosis has been reported to be extremely rare in Japan, as compared with European countries. There are few reports discussing the correlation of portal vein thrombosis with refractory ascites. Between January 1994 and December 1995, 20 cases (91%) of 22 patients with liver cirrhosis with ascites admitted to our hospital responded well within 2 months to a combination therapy of diuretics and albumin infusion, and the other two cases (9%) with refractory ascites were associated with portal vein thrombosis. The ascites in the first patient continued for 1 year, despite diuretics and albumin infusion therapy, and portal vein thrombosis was confirmed by autopsy. The ascites in the other patient continued for more than 4 months, and portal vein thrombosis was detected by ultrasound. Portal vein thrombosis was not found in the other 20 cirrhotic patients with ascites. These two cases suggest that portal vein thrombosis may be a contributing factor to refractory ascites in patients with decompensated liver cirrhosis.     

Splenic vein thrombosis with pancytopenia and fever: antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is now recognized as one of the most important causes of hypercoagulability. The most common site for venous thrombosis in APS is deep venous thrombosis of the lower extremities. Other sites of venous thrombosis include retinal veins, renal veins, and hepatic veins. The authors report a case of splenic vein thrombosis disclosing antiphospholipid syndrome in which also the cytolytic effect of aPL may play a role of "cofactor" in the genesis of thrombosis through the release of thromboplastin from the lysis of red cells, granulocytes and platelets, making them vulnerable to clearance by splenic macrophages. Important considerations are stressed about differential diagnosis, etiopathogenetic factors, therapy and follow-up of the patient.     

Clinical manifestations associated with antiphospholipid antibodies

The antiphospholipid antibodies are immunoglobulins able to join negative charge phospholipids. The have been related to a great variety of conditions, specially among connective tissue illness although the idiopathic form seems to be the most frequent. Their presence must be ruled out in cases of young patients with stroke, deep veins thrombosis, acute heart attack and woman suffer multiple abortions and foetal death. These antibodies appear to be related to different clinical entities like Sneddon syndrome. Evans syndrome, "chorea gestationis", migraine. The laboratory determinations are based in direct methods (ELISA, RIA, ...) as well as in indirect ones (activated partial thromboplastin time, reptilase time, ...). The appropriate management and treatment may be based upon clinical expression, in case of arterial thrombosis (type II APS), or deep vein thrombosis (Type II) long term anticoagulation is indicated; Association with pentoxifylline in the case of retinal thrombosis (type IIIa), Stroke (type IIIb) cases may require long term anticoagulation as well as aspirin. Type IV cases are better managed with an individualised treatment.     

Coronary thrombosis. Effects of blood flow on the mechanism of thrombus formation

The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.     

Case report: acute renal vein thrombosis in patients with spinal cord injury and secondary amyloidosis

Chronic spinal cord injury, when complicated by chronic suppurative infections, has replaced chronic tuberculosis as a leading cause of secondary amyloidosis. Renal involvement with secondary amyloidosis is characterized by the presence of nephrotic range proteinuria and an increased incidence of renal vein thrombosis. Two cases of acute renal vein thrombosis associated with secondary amyloidosis in patients with spinal cord injury are presented. In both cases, a past history of extensive decubitus ulcerations and urinary tract infections preceded the development of nephrotic range proteinuria. In case 1, nonoliguric acute renal failure occurred after the development of acute bilateral renal vein thrombosis. The patient declined dialytic therapy and expired with uremia. In case 2, worsening renal function and increased proteinuria resulted after the development of acute unilateral renal vein thrombosis. These cases include the clinical and anatomic findings of acute renal vein thrombosis that occur as a complication of secondary amyloidosis. Acute renal vein thrombosis should be considered whenever an acute change in renal function or increase in proteinuria is noted in this setting.     

Recognition, diagnosis, and management of heparin-induced thrombocytopenia and thrombosis

This case report describes a post-coronary artery bypass graft patient who developed arterial thrombosis and loss of a dominant hand as a result of the common and serious immune complication of heparin anticoagulation, heparin-induced thrombocytopenia and thrombosis. This report underscores the need for all surgeons who use heparin in the course of their practice to be aware of heparin-induced thrombocytopenia and the spectrum of its clinical presentations and management. Thrombocytopenia or thrombosis that occurs in a patient receiving heparin should prompt a surgeon to stop all heparin as soon as possible and seek appropriate hematologic consultation. Because heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis are mainly clinical diagnoses, one should not wait for objective test confirmation of heparin-induced thrombocytopenia before stopping all heparin treatment. Alternative anticoagulation, other than low molecular weight heparin, must be considered for the patient who develops either condition. For surgeons who perform hand surgery, it is necessary to be aware of the significance of upper extremity thrombosis in a patient who is receiving heparin when consulted for surgical management.     

Value of CT-angiography in diagnosis of cerebral sinus and venous thromboses

Dural sinus thrombosis is not uncommon. Due to the nonspecific symptomatology, as well as the manifold etiology, clinical diagnosis may be difficult. In these cases imaging procedures are frequently crucial in deciding how to proceed and how to treat. The aim of our study was to evaluate the diagnostic utility of helical CT in the detection of dural sinus thrombosis. In 20 patients with clinically suspected thrombosis CT angiography was performed. In 6 patients dural sinus thrombosis was diagnosed. In order to acquire also arterial vessels, a short delay of about 22 s after the onset of the application of contrast medium was selected. By this method we found an occlusion of the MCA in two patients with clinically suspected sinus thrombosis. In all patients the transverse slices and the multiplanar reconstructions showed filling defects or an "empty delta" sign. With irregular outlines the thrombus could be depicted over the complete course of the sinus. The MIP reconstructions were particularly helpful in the evaluation of the vessel anatomy and the pathological collateral venous drainage. In three patients MR angiograms were available for comparison. The smaller veins, such as the v. vermis inferior, were less clearly depicted than in CT angiography. CT angiography is a fast and reliable method to exclude or verify a sinus thrombosis. It can be performed immediately after non-enhanced CT. According to our present experience CT angiography is sufficient for the diagnosis of a sinus thrombosis.     

Efficacy and safety of low molecular weight heparin in renal transplantation

BACKGROUND: Deep venous thrombosis (DVT) is a common problem with potentially devastating results in patients undergoing major surgical procedures. Certain renal transplant recipients are particularly at risk for allograft loss as a consequence of renal vein and artery thrombosis. Over the past few years, low molecular weight heparin has been well established as an accepted modality of treatment and prophylaxis of DVT. The efficacy and safety of low molecular weight heparin in the prophylaxis of DVT following renal transplantation in adults has not previously been reported. METHODS: Dalteparin was administered to 120 adult renal transplant recipients postoperatively at the Oregon Health Sciences University. RESULTS: No patient developed allograft arterial or venous thrombosis. One patient developed subclavian vein thrombosis. No bleeding complications were encountered, and side effects were very minimal. CONCLUSION: Prophylaxis with dalteparin is an effective and safe modality for the prevention of thrombosis in adult patients undergoing renal transplantation.     

P-pills and thrombosis

This review provides an account of the present situation as reflected by findings in recent studies, which illustrate epidemiological, clinical and metabolic aspects of thrombosis associated with oral contraceptive (OC) usage. With the reduction of the oestrogen content of OCs, the relative risk for acute myocardial or cerebral thrombosis is now 1.5-3. Low-dose OCs containing third generation gestagens seem to be associated with less risk of infarction, and possibly of cerebral thrombosis, than are OCs containing second generation gestagens. The risk of venous thrombosis is increased 2-4-fold in conjunction with the usage of low-dose OCs with second generation gestagens, and possibly slightly more (3-5-fold) in conjunction with OCs containing third generation gestagens, though this is of small clinical significance. When prescribing OCs for women at an increased risk of venous thrombosis, a low-dose pill with a second generation progestagen seems to be preferable. If OCs are prescribed to women at an increased risk of arterial thrombosis, OCs with third generation progestagens seem to be a reasonable first choice. Women with no thrombotic predisposion can safely use any type of low-dose OCs [corrected].     

Levels of tumor necrosis factor alpha, gamma interferon, and interleukins 4,6, and 10 as determined in mice infected with virulent or attenuated strains of Trypanosoma cruzi

The incidence of puerperal ovarian vein thrombosis is estimated to range between 1 in 600 and 1 in 2000 deliveries. The cardinal signs of puerperal ovarian vein thrombosis include fever, leukocytosis, and right lower quadrant abdominal pain, most often in a recently delivered female patient. These patients are classically described as failing to improve with intravenous antibiotic therapy alone; resolution of symptoms and presumptive diagnosis is made on defervescence with the addition of intravenous heparin therapy. Objective diagnostic modalities include venography, ultrasound, laparoscopy, and MRI, although CT remains the gold standard for the identification of this under-diagnosed entity. We present a case report of a 20-year-old female treated at our facility for puerperal ovarian vein thrombosis. She was transferred to our vascular surgery service after developing the classic signs of puerperal ovarian vein thrombosis and undergoing CT demonstrating ovarian vein thrombosis with extension of free-floating thrombus into her inferior vena cava (IVC). This degree of thrombosis was particularly concerning when one considers the 3 to 33 per cent rate of pulmonary embolism reported in patients with puerperal ovarian vein thrombosis. Treatment modalities for such extensive degrees of thrombosis are described in the literature and range from hysterectomy and thrombectomy to ligation of the IVC. In our case, we prophylactically placed a suprarenal IVC Greenfield filter to protect against pulmonary embolism and proceeded with the standard regimen of anticoagulation and antibiotics. This treatment approach has been reported only twice previously in the literature, to our knowledge.     

Predicting the occurrence of adverse events after coronary artery bypass surgery

Approximately 15% of patients with mitral valve disease will experience left atrial thrombosis and its consequences. The etiology and diagnosis of left atrial thrombosis are reviewed, stressing the importance of blood stagnation as the most important etiologic factor. Atrial fibrillation, a left atrial diameter greater than 60 mm and absence of significant mitral regurgitation are predictors of left atrial thrombosis in mitral stenosis. Left atrial thrombus can be detected in 50% of patients with all three factors; all influence blood stagnation. Smoke-like echoes in the left atrium, detected by echocardiography, provide a semi-quantitative assessment of left atrial blood stagnation. The incidence of thrombi in patients with well marked smoke-like echoes is 60%, while in those without this echocardiographic finding it is only 9%. Smoke-like echoes provide an early warning system of conditions in the left atrium likely to lead to thrombosis unless the patient is anticoagulated.     

Isolated cortical venous thrombosis and ulcerative colitis

Aseptic cortical venous thrombosis is rare without concomitant dural sinus thrombosis. Ulcerative colitis is associated with both dural sinus thrombosis and isolated cortical venous thrombosis. We describe a 26-year-old woman with ulcerative colitis who had a spontaneous cerebral hemorrhage. An overlying thrombosed cortical vein was identified on spin-echo MR images and confirmed with angiography. Signal characteristics of thrombosed cortical veins are similar to those described in dural sinus thrombosis.     

The prevention of postoperative deep vein thrombosis and pulmonary embolism with low dose subcutaneous heparin and dextran

The standard low dose of heparin for the prevention of deep venous thrombosis in patients who are operated upon is 5,000 units administered subcutaneously two hours before operation and at eight or 12 hourly intervals for the next seven days. Heparin in low doses can at present be recommended as an effective agent in the prevention of deep venous thrombosis in patients over the age of 40 years who are undergoing a major abdominothoracic or gynecologic operation. There is reasonable evidence that heparin in low doses also offers a satisfactory protection against fatal pulmonary embolism for patients at high risk after general abdominothoracic operations. The evidence of the effectiveness of low doses of heparin in the prevention of deep venous thrombosis is less well established in other patients and particularly those at high risk, as after urologic and hip operations. This important distinction is to be made in terms of the population at risk and the efficacy of heparin in low doses. Considering the evidence so far available, it appears that the postoperative state in which dextran has been shown to reduce the incidence of phlebographically confirmed deep venous thrombosis most convincingly is after orthopedic operations. Major orthopedic operations are precisely the type in which the superiority of heparin in low doses is controversial. Unless proved otherwise, dextran 70 in an infusion of 500 to 1,000 milliliters of a 6 per cent solution started before operation and 500 milliliters the following and next three alternate days may be the agent of choice in preventing deep venous thrombosis in major orthopedic operations. Using this scheme, the prophylaxis of postoperative deep venous thrombosis appears equally effective with dextran 70 as with oral anticoagulants. Whether the protection offered by dextran 70 will also prevent fatal and nonfatal pulmonary embolism is still an open question. Low doses of heparin and dextran do not expose patients to serious risks of bleeding after operation, and with the recommended doses of the latter drug, other untoward effects are rare. At the doses recommended, neither of these two drugs requires laboratory monitoring.     

Thrombosis of the cerebral vessels following closed cranial trauma (author's transl)

The case histories are presented of 6 patients, 5 of whom developed carotid artery thrombosis (the left vessel being affected in 4 cases and the right only in 1 case) following closed cranio-cerebral trauma; the 6th patient developed thrombosis of the posterior cerebral artery, as confirmed at autopsy. The factors involved in the aetiology of these events are discussed on the basis of the case reports.     

Risk factors for venous thrombosis: prevalence, risk, and interaction

Annually, 1 in 1,000 individuals is affected by venous thrombosis. Risk factors that are known to increase the risk of thrombosis may be either genetic or acquired, or have a combined origin. Many of these risk factors are very frequent, among which several have been recently identified, such as resistance to activated protein C by factor V Leiden, hyperhomocysteinemia, high levels of factors VIII, as well as the classical acquired risk factors, such as surgery and malignancies. When the prevalence of risk factors is high, it becomes likely that in some individuals two or more risk factors will be present simultaneously. The question "What happens to the risk in these circumstances?" is one involving interaction, also known as effect modification or synergy. In this article we review the prevalence and risk estimates for the various genetic and acquired risk factors for venous thrombosis, discuss the concept of interaction, and give an overview of the evidence for interaction of these risk factors.     

Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis of the native kidney

OBJECTIVE: Previous studies of transplant kidneys and recent reports on native kidneys have suggested intrarenal arterial Doppler findings can be helpful in the noninvasive workup of renal vein thrombosis. We used arterial Doppler sonography to evaluate cases of possible acute renal vein thrombosis in native kidneys that had equivocal results on standard Doppler analysis of the renal vein. MATERIALS AND METHODS: Twenty native kidneys in 12 patients with clinical findings suggestive of acute renal vein thrombosis had Doppler studies of the main renal vein that failed to show normal flow. In all 20 kidneys, duplex Doppler study of arcuate/interlobar intrarenal arteries was done and the resistive index was determined. The Doppler findings were compared with subsequent findings on either renal venograms (n = 11) or MR images (n = 9), which served as the reference "gold" standards. RESULTS: The prevalence of renal vein thrombosis was 25% (5/20). Ten kidneys had very abnormal findings on arterial Doppler studies (absent or reversed end-diastolic flow), but only two of these were proved to have renal vein thrombosis. In six other kidneys, end-diastolic flow was identified but the resistive index was still elevated (> or = 0.70), and only one of these kidneys was proved to have renal vein thrombosis. Four kidneys had normal arterial Doppler studies, and 50% (two) of these were proved to have renal vein thrombosis. When absent or reversed end-diastolic flow was used as a sign of renal vein thrombosis, intrarenal arterial Doppler analysis had a sensitivity of 40% (2/5) and a specificity of 47% (7/15). CONCLUSION: Unlike the reported experience in transplanted kidneys, intrarenal arterial Doppler analysis is neither sensitive nor specific for renal vein thrombosis in native kidneys. An intrarenal arterial Doppler study with normal findings should not prevent further workup if Doppler findings in the renal vein are equivocal, nor should absent or reversed end-diastolic arterial signals be considered highly suggestive of renal vein thrombosis.     

IL-10 regulates thrombus-induced vein wall inflammation and thrombosis

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.     

Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies

Antiphospholipid antibodies (aPL) characterize patients at risk for both arterial and venous thrombotic complications. Recently it has been recognized that the presence of plasma proteins such as beta 2-glycoprotein I(beta 2 GPI) and prothrombin are essential for the binding of aPL to phospholipids and that these proteins are probably the real target of aPL. The discovery of these new antigens for aPL introduces the possibility of new assays to detect the presence of aPL. However, it is not known whether these assays improve the identification of patients at risk for thrombosis. In this retrospective study we compared the value of the classic assays LAC (lupus anticoagulant) and ACA (anticardiolipin antibodies) to detect aPL associated with thrombotic complications, with new assays which are based on the binding of aPL to the plasma proteins prothrombin and beta 2GPI. To do so, we have used these assays in a group of 175 SLE patients and correlated the positivity of the different assays with the presence of a history of venous and arterial thrombosis. Control groups were patients without SLE but with LAC and/or ACA and thrombosis (n = 23), patients with thrombosis without LAC and ACA (n = 40) and 42 healthy controls. In the univariate analysis, in which no distinction has been made between high and low antibody levels, we confirmed LAC and ACA to be related to both arterial and venous thrombosis. Anti-beta 2GPI- and anti-prothrombin-antibodies, both IgG and IgM correlate with venous thrombosis and anti-beta 2GPI-IgM with arterial thrombosis. Multivariate analysis showed that LAC is the strongest risk factor (OR 9.77; 95% CI 1.74-31.15) for arterial thrombosis. None of the other factors is a significant additional risk factor. For venous thrombosis LAC is the strongest risk factor (OR 6.55; 95% CI 2.36-18.17), but ACA-IgM above 20 MPL units also appeared to be a significant (p = 0.0159) risk factor (OR 3.90; 95% CI 1.29-11.80). Furthermore, the presence of anti-beta 2GPI- and/or anti-prothrombin-antibodies in LAC positive patients (n = 60) does not increase the risk for thrombosis. The results showed that (i) the LAC assay correlates best with a history of both arterial and venous thrombosis and (ii) neither the anti-beta 2GPI ELISA nor the anti-prothrombin ELISA gives additional information for a thrombotic risk in SLE patients.