Thrombosis Syndrome Research Articles

Abstract 497: Clinical Significance of Heparin Induced Thrombocytopenic Thrombotic Syndrome with Initiation of Anti-heparin Antibodies Negative: A Case Report and Literature Review

Introduction Heparin induced thrombocytopenia thrombosis Syndrome has a high mortality and morbidity in cardiac surgical patients in spite of early diagnosis and management. We present a case with multiple acute deep venous thrombosis (DVT) after using unfractionated heparin (UFH) during coronary artery bypass graft (CABG) with initiation of HIT antibodies negative. Case presentation A 70-year-old male complained of left leg pain 2 days after CABG for an acute ST-elevation myocardial infarction. Patient was treated with UFH intravenous during CABG. Platelet count was 78 x 109/L that was 130 x 109/L before the procedure. Anti-heparin antibodies IgM/IgG were negative. Venous Doppler ultrasound showed an acute deep venous thrombosis (DVT) in the left peroneal vein. However, after the patient was treated with Coumadin anticoagulation for 7 days with INR in therapeutic range (2-3), the patient presented for right low extremity pain. Platelet count was 40 x 109/L. Anti-heparin antibodies IgM and IgG were repeatedly positive. Venous Doppler ultrasound showed multiple bilateral lower extremities acute DVTs. Patient had thrombectomy and continued with coumadin anticoagulation at INR in therapeutic range for 3 months. Discussion HITTS is an immune-mediated drug reaction that occurs more frequently in patients undergoing cardiovascular surgery. Thrombosis caused by the HIT/T syndrome is most commonly venous thromboembolism. Thrombosis is arterial in about 20% of cases, including acute limb ischemia, myocardial infarction, or stroke. Previous clinical data has shown that about 40% of high titer-negative HIT antibodies were associated with a positive result in repeated testing several days later, which is the same as our presentation. The mortality and morbidity rates of HITTS are approximately 30% and 60%, respectively, and an additional ~10% of patients require amputations or suffer other major morbidity. However, with early recognition and intervention, mortality can be reduced from >30 to <10%. Obviously, repeated testing to identify patients who have HIT despite a negative initial HIT test in several days is greatly recommended. Diagnosis is essentially clinical and negative results from laboratory assays do not exclude the diagnosis.

Antiphospholipid Syndrome Antibodies — Snippets from the Laboratory

Antiphospholipid (aPL) antibodies refer to antibodies associated with the clinical syndrome of vascular thrombosis and/or pregnancy morbidity, termed as aPL syndrome (APS). aPL antibodies include lupus anticoagulants (LA), anticardiolipin (aCL) antibodies and anti-β2-glycoprotein 1 (anti-β2GP1). aCL antibody is more sensitive than LA and anti-β2GP1 even though the latter are more specific for APS. Interpretation of aPL results should be done collectively together with the clinical presentation of each individual. The latest recommendations and consensus on aPL antibody testings should be closely adhered to by laboratories in order to achieve an accepted standard and to ensure accuracy of test results.

Heparin-Induced Thrombocytopenia in Chinese Patients: 240 Patients Study in One Center

The study was conducted in order to analyze the incidence of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) in 240 patients from the Department of Vascular Surgery in China, to evaluate the current laboratory detection technique, and to explore the feasibility for the technique to be developed in China. 240 patients receiving unfractionated heparin (UFH) were studied in one center. Before and after the UFH treatment, platelet count, HIT-antibody ELISA test, and heparin-induced platelet aggregation (HIPA) were tested. Among 240 patients, HIT was diagnosed in 36 cases. The incidence was 15%. HITTS occurred in 6 cases (2.5%). The median time of thrombocytopenia was the 8th day. Platelet counts recovered to normal level in 3 - 6 days after heparin withdrawal The incidence of HIT is higher; however, the incidence of HITTS is lower. Monitoring platelet count, which is simple and easy to do and available in hospitals at different levels (township hospital included), is a reliable method to diagnose HIT early. The HIT-antibody ELISA test could be introduced in specific hospitals to prescreen HIT. In view of the higher sensitivity and specificity of HIPA, it can be used in larger diagnostic centers in all the big cities of China.

Purpura Fulminans following Thermal Injury

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin, which is an unusual cutaneous manifestation of disseminated intravascular coagulation. It often occurs in small children and babies due to infection and/or sepsis, rarely in adults in clinic. We report the first case of deadly purpura fulminans following thermal injury in a 64-year-old Chinese woman. The purpura developed sharply and aggravated multiple organ dysfunction. The patient died of purpura fulminans, disseminated intravascular coagulation, and multiple organ dysfunction syndrome.

Paget-schroetter Syndrome- A Case Report

A rare case of primary upper-extremity deep vein thrombosis or Paget-Schroetter syndrome is reported. It is effort thrombosis usually affecting young healthy individuals and is a rare condition. Our patient was a middle aged male daily laborer with history of exertion using the right upper limb. He responded to limb elevation and anticoagulation. No other cause for thrombosis was found.

Resection of a giant bilateral retrovascular intrathoracic goiter causing severe upper airway obstruction, 2 years after subtotal thyroidectomy: a case report and review of the literature.

The intrathoracic (or substernal) goiter is more often benign; but it can be malignant in 2-22% of patients. There is history of prior thyroid surgery in 10% to more than 30% of patients. Intrathoracic goiters cause adjacent structure compression more frequently than the cervical goiters, due to the limited space of the thoracic cage. Compression of trachea, oesophagus, vascular and neural structures may cause dyspnoea, dysphagia, superior vena cava syndrome, subclavian vein thrombosis, hoarseness, and Horner's syndrome. There is usually progressive deterioration, but acute exacerbation may occur. The presence of a thoracic goiter (>50% of the mass below the thoracic inlet) is per se an indication for resection. Tracheal compression by (cervical or thoracic) goiter is also an indication for resection; early tracheal decompression is recommended particularly in symptomatic patients. In severe respiratory distress, intubation and semi-urgent operation may be required. With early intervention, most intrathoracic goiters can be removed through a cervical approach, while tracheomalacia is avoided. We hereby present successful and uncomplicated total thyroidectomy, through a median sternotomy, of a benign, gigantic, bilateral, retrovascular, posterior mediastinal, intrathoracic goiter, encircling the trachea, and causing severe respiratory distress in a 63 year old man with history of previous subtotal thyroidectomy.

Ansprüche des Nephrologen an den guten Dialysezugang

Vascular access is the lifeline of hemodialysis patients. The superiority of autogenous arteriovenous fistulas compared to prostethic arteriovenous grafts or a central venous catheter is well established. Fistulas have a far lower risk of failure and a reduced requirement for revision compared to prosthetic grafts. Alternative vascular access can be achieved via a prosthetic graft or permanent central venous catheter but the risk of infection is increased. The most important complications are shunt thrombosis, stenosis, aneurysms or steal syndrome. Signs of these complications should be recognized by the dialysis team and early surgical intervention can avoid major complications. In many cases a complex shunt is necessary if the patient has been on dialysis for a long time. Interaction between the dialysis team, nephrologists, surgeons and interventional radiologists can improve the prognosis of dialysis patient.

Purpura Fulminans Associated with Streptococcus pneumoniae Septicemia in an Asplenic Pediatric Patient

Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans.

Coqueluche grave,e volución y exanguino transfusión como tratamiento alternativo. Serie de casos

Pertussis is a contagious disease that may develop a serious clinical picture by hypoxemia and pulmonary hypertension refractory to treatment. The syndrome of hyperviscosity and arteriolar thrombosis is responsible for the cardiocirculatory collapse. Our objective is to describe the evolution of a series of patients with severe pertussis, some of whom received exchange transfusion (ET) as an alternative treatment. We analyzed 41 patients' clinical charts with diagnosis of pertussis treated in the Pediatric Intensive Care Units during the 2003-2011 period. The mean age was 2.38 months. In the 90.2% of cases, the cause of admission to PICU was respiratory failure; 75% required mechanical respiratory support and 39% developed pulmonary hypertension. The overall mortality was 41.4%. Nine patients were treated by ET, 5 died. Conclusion. Severe pertussis is associated with high mortality. ET reduced the mass of circulating leukocytes in 53.5%; ET could be an alternative to conventional treatment, although controlled studies are required to assert it.

Minimally invasive plate osteosynthesis in the treatment of multifragmentary fractures of the proximal tibia

Background Proximal tibia fractures with metaphyseal comminution present a difficult treatment challenge. Minimally invasive plate fixation (osteosynthesis) (MIPO) has theoretical advantages for the treatment of these injuries. This report presents the clinical results of the MIPO system for the treatment of a series of patients with complex proximal tibia fractures. Patients and methods Between March 2003 and February 2007, 28 consecutive patients with comminuted proximal tibia metaphyseal fractures with intra-articular extension were treated with MIPO in Benha Faculty of Medicine. The mean age of the patients was 37 years (range between 21 and 60 years). There were 22 closed fractures and six grade I open fractures (Gustilo Anderson classification). Results The average follow-up was 23 months (range 12–48). In 26 (92.8%) out of 28 patients, the fracture heeled after the index procedure and had satisfactory results. One patient had a fair result because of valgus malalignment and replating was performed. One patient had a poor result because of deep infection and loosening. Postoperative fracture alignment was satisfactory in 26 out of the 28 cases and was maintained in all patients at union. There was no deep venus thrombosis or compartment syndrome. Conclusion The MIPO can be used safely to treat complex proximal tibia fractures without the need for additional medial stabilization. Surgeons attempting to use MIPO should familiarize themselves with the significant technical differences between these and traditional plating systems to ensure satisfactory results.

Molecular Imaging of Fibrin Deposition in Deep Vein Thrombosis Using Fibrin-Targeted Near-Infrared Fluorescence

The goal of this study was to develop and validate a new fibrin-targeted imaging agent that enables high-resolution near-infrared fluorescence (NIRF) imaging of deep vein thrombosis (DVT). NIRF imaging of fibrin could enable highly sensitive and noninvasive molecular imaging of thrombosis syndromes in vivo. A fibrin-targeted peptide was conjugated to a near-infrared fluorophore Cy7, termed FTP11-Cy7. The NIRF peptide is based on a fibrin-specific imaging agent that has completed Phase II clinical magnetic resonance imaging trials. In vitro binding of FTP11-Cy7 to human plasma clots was assessed by using fluorescence reflectance imaging. Next, FTP11-Cy7 was intravenously injected in mice with femoral DVT induced by topical 7.5% ferric chloride treatment. Intravital fluorescence microscopy and noninvasive fluorescence molecular tomography-computed tomography were performed in 32 mice with DVT, followed by histological analyses. In vitro human clot-binding analyses showed a 6-fold higher NIRF clot target-to-background ratio (TBR) of FTP11-Cy7 than free Cy7 (6.3 ± 0.34 vs. 1.2 ± 0.03; p < 0.0001). The thrombus TBR of acute and subacute femoral DVT with FTP11-Cy7 obtained by using intravital fluorescence microscopy was >400% higher than control free Cy7. Binding of FTP11-Cy7 to thrombi was blocked by a 100-fold excess of unlabeled competitor peptide both in vitro and in vivo (p < 0.001 for each). Histological analyses confirmed that FTP11-Cy7 specifically accumulated in thrombi. Noninvasive fluorescence molecular tomography-computed tomography imaging of fibrin in jugular DVT demonstrated strong NIRF signal in thrombi compared with sham-operated jugular veins (mean TBR 3.5 ± 0.7 vs. 1.5 ± 0.3; p < 0.05). The fibrin-targeted NIRF agent FTP11-Cy7 was shown to avidly and specifically bind human and murine thrombi, and enable sensitive, multimodal intravital and noninvasive NIRF molecular imaging detection of acute and subacute murine DVT in vivo.

ThrombusObliteration byRapidPercutaneousEndovenous Intervention inDeep VenousOcclusion (TORPEDO) Trial:Midterm Results

To present midterm results from a randomized study comparing the safety and efficacy of percutaneous endovenous intervention (PEVI) + anticoagulation vs. anticoagulation alone in the reduction of venous thromboembolism (VTE) and post-thrombotic syndrome (PTS) in acute symptomatic proximal deep venous thrombosis (DVT). The TORPEDO trial was a randomized study to demonstrate superiority of PEVI in the reduction of the VTE and PTS at 6 months; in that trial, 183 patients (103 men; mean age 61 ± 11 years) with symptomatic proximal DVT were randomized to receive PEVI + anticoagulation (n = 91) or anticoagulation alone (n = 92). PEVI consisted of one or more of a combination of thrombectomy, balloon venoplasty, stenting, and/or local low-dose thrombolytic therapy. At 6 months, recurrent VTE developed in 2.3% of the PEVI + anticoagulation group vs. 14.8% in the anticoagulation only group (p = 0.003); PTS developed in 3.4% vs. 27.2% (p<0.001), respectively. At a mean follow-up of 30 ± 5 months (range 12-41), 88 patients in the PEVI + anticoagulation group and 81 patients in the anticoagulation only group reached target follow-up. Recurrent VTE developed in 4 (4.5%) of the 88 PEVI + anticoagulation patients vs. 13 (16%) of the 81 patients receiving anticoagulation only (p = 0.02). PTS developed in 6 (6.8%) of the PEVI + anticoagulation group vs. 24 (29.6%) of the anticoagulation only group (p<0.001). In patients with proximal DVT, PEVI is superior to anticoagulation alone in the reduction of VTE and PTS. This benefit, which appears early in the course of treatment, extends to >2.5 years.

Allograft Coronary Artery Thrombosis: A Case Report of Early Cardiac Allograft Left Ventricular Myocardial Infarction

Cardiac allograft dysfunction is a major cause of morbidity and mortality in the early post-transplantation period. This is a critical condition that requires prompt diagnosis and management. We present the case of a 57-year-old man with ischemic cardiomyopathy who underwent cardiac transplantation and developed a rare case of coronary artery thrombosis in the setting of heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) within the first 2 postoperative weeks. Transmural myocardial infarction (MI) was initially noted on cardiac magnetic resonance (CMR) imaging as regional left ventricular wall motion abnormalities and transmural hyperenhancement after gadolinium administration, prompting further evaluation of the coronary circulation with angiography.

Fondaparinux-Associated Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immune-mediated clinical syndrome of thrombocytopenia and thrombosis occurring after exposure to heparin. HIT most commonly occurs after exposure to unfractionated heparin but has also been reported with low-molecular-weight heparin. To date, there have been very few reports of HIT with the pentasaccharide fondaparinux, and some have proposed fondaparinux as a treatment for HIT. This article presents two cases of HIT associated with fondaparinux use.

Spectrum of purpura fulminans: Report of three classical prototypes and review of management strategies

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin that is rapidly progressive and is accompanied by vascular collapse and disseminated intravascular coagulation. It usually occurs in children, but this syndrome has also been noted in adults. The three forms of this disease are classified by the triggering mechanisms. We describe three classical cases of purpura fulminans of the three classical prototypes treated at our center and their varied clinical outcomes. We also describe a case of acute infectious purpura fulminans secondary to systemic leptospirosis which to our best knowledge is the first reported case in world literature. The various treatment options for purpura fulminans have also been reviewed.

Extrinsic compression of left iliac vein does not predict the development of post thrombotic syndrome in left side deep venous thrombosis

PurposeLeft side deep venous thrombosis (DVT) is associated with May-Thurner's anatomical variation and is often instigated by invasive treatment. The aim of this study is to analyze the influence of left iliac vein narrowness on incidence of post thrombotic syndrome (PTS) that developed after left side DVT.MethodsForty-one left side DVT cases that were followed up for more than 1 year were enrolled. The iliac vein narrowness was measured by the shortest distance from the right iliac artery to the 5th lumbar vertebra overlying left iliac vein in computed tomography (CT) scan. The incidence of PTS was measured by phone-call history taking for specific symptoms of PTS. The means of the shortest distance were compared by independent t-test.ResultsThe number of PTS cases was eleven (26.8%). The level of thrombus, demographic data and other risk factors were similar in both PTS and non-PTS groups except the mean risk factor score. The mean of the shortest distance of PTS group and non-PTS group were 5.56 mm and 5.89 mm, respectively.ConclusionThe degree of left iliac vein narrowness measured by the shortest distance from the right iliac artery and the 5th lumbar vertebral body was not a predictive factor for PTS.

Thunderclap headache as the primary clinical feature of a supratentorial embolic cerebral infarct

A formula for the diagnostic assessment of thunderclap headache (TCH) should be established. The management of this type of headache is controversial. The established diagnostic assessment of TCH includes a computer tomography (CT) of the head and cerebrospinal fluid (CSF) examination to exclude a subarachnoid haemorrhage. In patients whose CT scans and CSF analyses are normal, further testing is rarely considered to be indicated by most clinicians [1]. However, others suggest that in circumstances where CT and CSF are normal, further diagnostic assessment with magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) of the brain and neck, and magnetic resonance venography is necessary [2]. Articles differ in their conclusions and recommendations. A MRI-verified supratentorial embolic cerebral infarct with TCH as the primary clinical feature is to my knowledge not hitherto reported. Here is described a patient who experienced a TCH as the primary clinical feature of an embolic insula/temporal lobe infarct. A 41-year-old woman appeared in the emergency department following an acute and sudden onset of severe headache. The pain was located in the left temporal region, it reached its maximum intensity in \1 min and lasted for about 7 h. At the time of admission to hospital, the patient reported that the headache had waned. There was no previous history of headaches. Vital signs and physical examination were normal. Neurological examination was normal. Laboratory testing was within the normal range. Blood pressure monitoring was normal. An electrocardiogram (ECG) showed sinus rhythm. Cerebrospinal fluid (CSF) examination revealed a normal opening pressure (140 mmH2O), a normal closing pressure, a normal cell count, glucose and protein. Spectrophotometry disclosed no bilirubin. A CT scan of the head was normal. A magnetic resonance imaging (MRI) of the brain was carried out to exclude other causes of TCHs. It revealed an acute ischaemic lesion in the left insula/ temporal lobe (Fig. 1). A magnetic resonance angiography (MRA) was ordered to exclude intracranial aneurysms, cerebral venous thrombosis, dissection and reversible cerebral vasoconstriction syndrome. These investigations revealed an acute embolic occlusion of a main M2 segment branch of the left middle cerebral artery (Fig. 2). No dissection, reversible cerebral vasoconstriction syndrome or other abnormalities could be detected. Further investigations with ECG telemetry and echocardiography were normal. An additional MRI and MRA of the cervical arteries/intracerebral circulation 2 days later confirmed the cerebral infarct and the occlusion. An extensive laboratory testing revealed normal results. No source of the cerebral embolus could be found. The patient could be discharged and remains well. At follow-up after 6 months, she reported no headache. TCH is a very rare manifestation of a cerebral infarct. In 2006, a case report was published where a TCH was the presenting clinical feature of embolic cerebellar infarcts, in the absence of neurological findings [3]. Gossrau et al. [4] presented a similar case (cerebellar infarct) in 2008. Headache is not uncommon in ischaemic stroke, but is usually overshadowed by other manifestations such as aphasia and neglect [5]. It is usually focal and mild [5]. The character of the headache is throbbing [5]. The severity of the headache is not related to the size of the infarct or the location of the lesion [5]. B. Edvardsson (&) Department of Neurology, Faculty of Medicine, Lund University Hospital, 221 85 Lund, Sweden e-mail: Bengt.Edvardsson@med.lu.se

The Role of Nanomedicine in The Imaging and Therapy of Thrombosis

Hemostasis is the mechanism by which the body prevents blood loss. In its absence, even the smallest trauma would result in the need for immediate intervention to prevent life-threatening hemorrhage, as is seen in coagulation disorders, such as hemophilia. Thus, the formation of blood clots (thrombi) within vessels is a beneficial process as it prevents blood loss. However, in contradistinction to its beneficial effects to limit uncontrolled bleeding, exaggerated clotting can lead to pathological thrombus formation, which, depending on its location, may result in significant morbidity and mortality. Over a century ago, Virchow described three underlying factors in the pathogenesis of thrombosis: stasis, hypercoaguability and vascular injury. On the arterial side, thrombosis (often superimposed on athero sclerotic lesions and usually platelet rich) leads to end-organ ischemia, causing syndromes such as stroke, myocardial infarction and sudden cardiac death. On the venous side, red blood cell- and fibrin-rich thrombi cause the highly morbid deep venous thrombosis syndromes, as well as the potentially fatal syndrome of pulmonary embolism. Regardless of arterial or venous origin, the rapid diagnosis and treatment of pathological thrombosis is of the utmost importance, as restoration of vascular patency is associated with the best prognosis. In this regard, targeted nanomaterials may serve as excellent platforms on which to develop multifunctional agents for the unified detection and treatment of this disease.

CalDAG-GEFI deficiency protects mice in a novel model of FcγRIIA-mediated thrombosis and thrombocytopenia

AbstractPlatelet activation via Fcγ receptor IIA (FcγRIIA) is a critical event in immune-mediated thrombocytopenia and thrombosis syndromes (ITT). We recently identified signaling by the guanine nucleotide exchange factor CalDAG-GEFI and the adenosine diphosphate receptor P2Y12 as independent pathways leading to Rap1 small GTPase activation and platelet aggregation. Here, we evaluated the contribution of CalDAG-GEFI and P2Y12 signaling to platelet activation in ITT. Mice transgenic for the human FcγRIIA (hFcR) and deficient in CalDAG-GEFI−/− (hFcR/CDGI−/−) were generated. Compared with controls, aggregation of hFcR/CDGI−/− platelets or P2Y12 inhibitor-treated hFcR platelets required more than 5-fold and approximately 2-fold higher concentrations of a FcγRIIA stimulating antibody against CD9, respectively. Aggregation and Rap1 activation were abolished in P2Y12 inhibitor-treated hFcR/CDGI−/− platelets. For in vivo studies, a novel model for antibody-induced thrombocytopenia and thrombosis was established. FcγRIIA-dependent platelet thrombosis was induced by infusion of Alexa750-labeled antibodies to glycoprotein IX (CD42a), and pulmonary thrombi were detected by near-infrared imaging technology. Anti-GPIX antibodies dose-dependently caused thrombocytopenia and pulmonary thrombosis in hFcR-transgenic but not wild-type mice. CalDAG-GEFI-deficient but not clopidogrel-treated hFcR-transgenic mice were completely protected from ITT. In summary, we established a novel mouse model for ITT, which was used to identify CalDAG-GEFI as a potential new target in the treatment of ITT.

Nose and upper lip reconstruction for purpura fulminans

Purpura fulminans (PF) is a rare syndrome of intravascular thrombosis and haemorrhagic infarction of the skin. The initial symptom of PF is peripheral purpura which progresses to necrosis very rapidly. The prognosis of PF is poor, and the mortality is reported to be around 40%. Even if the patient survives, the patient may require amputation or reconstruction for limbs and facial necrosis. A 48-year-old male suffered from PF following a left cerebellopontine angle tumour excision. His nose and upper lip fell into necrosis afterwards. We performed nose and upper lip reconstruction at 8 months after the onset. We used a forehead flap for the nasal reconstruction and a free forearm flap for the lining. His upper lip was reconstructed with bilateral nasolabial orbicularis oris myocutaneous flaps. The colour and texture match of the reconstructed nose and lip is good. He could open his mouth wide enough and close completely. Facial reconstruction after PF is very difficult, because the patient has extensive scarring around the defect and there is little intact facial tissue. However, we performed a facial reconstruction using local flaps as much as possible, and obtained good results.