Multiple Thrombotic Events Research Articles

Lemierre Syndrome Associated with Streptococcus constellatus and Atypical Vascular Involvement: A Case Report and Review of the Literature

Background: Lemierre syndrome is a rare and life-threatening disease. It is characterized by septic thrombophlebitis of the internal jugular vein, historically associated with Fusobacterium necrophorum infection. However, atypical cases and associations with other organisms have been reported. Methods: Here, we describe a challenging case of Lemierre syndrome in a 71-year-old woman caused by Streptococcus constellatus and review the related literature. Case: The patient experienced multiple hospital admissions due to misdiagnoses and developed thrombosis involving the internal jugular vein and transverse sinus bilaterally, pulmonary complications including the formation of a pseudoaneurysm, and occipital abscess. She presented with headaches, neck pain, and blindness. Prolonged antibiotic therapy was administered, leading to gradual improvement of symptoms, with partial resolution of blindness. Prophylaxis with intramuscular penicillin was prescribed at discharge. Conclusions: Our case underscores the importance of considering Lemierre syndrome in patients who present with multiple thrombotic events affecting the intracranial circulation and/or jugular veins, particularly in those already receiving anticoagulation therapy or with no identifiable cause for thrombosis, even in the absence of sore throat or fever.

Unexpected normal ROTEM results in protein C deficiency with IVC thrombosis

Protein C deficiency is a hereditary disorder that increases the risk of thrombotic events but has unclear effects on rotational thromboelastometry (ROTEM) analysis. A man in his 60s with a history of protein C deficiency and multiple thrombotic events underwent inferior vena cava (IVC) filter removal, iliocaval thrombectomy and infrarenal IVC placement for IVC-related complete iliocaval and common femoral vein thromboses. A ROTEM analysis showed normal coagulation in NATEM and EXTEM and only a slight shortening in A10 and A20 in INTEM, which was unexpected given his diagnosis of protein C deficiency. Normal results indicate that there is complexity and variability of coagulation to maintain a balanced state even in individuals with underlying coagulation disorders.

Comprehensive secondary analysis of thrombotic events in pediatric patients receiving extracorporeal membrane oxygenation: A prospective cohort study.

This study aims to describe laboratory and clinical factors associated with thrombotic events during prolonged pediatric extracorporeal membrane oxygenation. A secondary analysis of a multi-center prospective study performed between 2012 and 2014. Patients under the age of 19years that received extracorporeal membrane oxygenation for at least 4days of therapy were included (n = 385). Univariable analysis and binomial regression were performed to evaluate predictive factors of single and multiple thrombotic events. A posteriori scoring tool was created to categorize thrombotic event severity. Over 39% of children receiving prolonged ECMO experienced a thrombotic event (TE). Binomial regression demonstrated an association between higher transfused platelet volume (mL/kg) (OR 1.04, CI: 95% 1.01-1.06, p = 0.003), Anti-Xa (OR 5.38, CI: 95% 1.22-23.8, p = 0.026) and aPTT (OR 1.01, CI: 95% 1.00-1.02, p = 0.032) the day prior to TE. Patients experiencing multiple TEs were associated with higher platelet transfusion volume (mL/kg) (OR 1.08, CI: 95% 1.05-1.12, p =< 0.001), antithrombin III (OR 1.03, CI: 95% 1.01-1.04, p = 0.001) and aPTT (OR 1.02, CI: 95% 1.01-1.03, p = 0.009). Patients experiencing multiple thrombotic events had a higher risk of 28-day mortality based on a cumulative clot severity score >4 (OR 2.37 (CI: 95% 1.32-4.24). Current lab tests show limited sensitivity to predict these events the day prior in a vulnerable patient group, leading to potential ECMO circuit failures. Patients with multiple thrombotic events during ECMO therapy face increased mortality risks, highlighting the need for dynamic reporting tools like clot severity scores and detailed documentation of interventions to enhance understanding and improve outcomes.

Thrombosis Tendency After Splenectomy in a Danish Family With Hemoglobin Volga, and a Literature Review

Hemoglobin (Hb) Volga is a rare, unstable β-chain hemoglobin variant (β27 Ala→Asp), causing chronic hemolytic anemia. This study presents two members of a Danish family, splenectomized due to Hb Volga at and with multiple thrombotic events. The proband was diagnosed with Hb Volga 9 years old and splenectomy was performed as a part of treatment. Throughout his life, he experienced multiple superficial thrombophlebitis, two episodes of distal deep venous thrombosis (DVT) on lower extremities (age 32 and 33) and a transient ischemic attack (TIA) presented as amaurosis fugax (age 51). Thrombophilia investigation was normal. The proband’s son was diagnosed with Hb Volga and underwent splenectomy at the age of 6. Despite anticoagulation therapy, he suffered from multiple venous thromboembolic events in his youth and died of chronic pulmonary embolism (PE)/pulmonary hypertension combined with infection. Given the observed propensity for multiple thromboses in these two patients, a literature review was conducted investigating reported occurrence of thrombotic events in individuals with Hb Volga. Currently 25 cases of Hb Volga are reported worldwide. The clinical symptoms primarily described are related to hemolytic anemia. Splenectomy is reported in 15 patients. Thromboses have previously been reported in only three patients who were also splenectomized. These cases involved DVT and PE, myocardial infarction, and an unspecified thrombotic event. The proband represents the first reported Hb Volga case with both venous and arterial thrombotic disorders. The exact mechanism underlying thrombotic tendency in patients with Hb Volga remains unknown, but it is probably associated with splenectomy.

Cannabis Usage and Prothrombotic Milieu: A Case Report of 38 years Old Cannabis Addict with Multiple Thrombotic Events

Cannabis Usage and Prothrombotic Milieu: A Case Report of 38 years Old Cannabis Addict with Multiple Thrombotic Events

Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome.

Thrombotic primary antiphospholipid syndrome (t-PAPS) is an acquired condition characterized by heterogeneous thrombotic manifestations, which is intriguing since venous and arterial thrombosis appear to have distinct pathogenesis. Gene expression analysis may constitute a new approach to evaluate potential similarities or differences between the clinical manifestations of t-PAPS. Recently, dysregulation of the ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression was associated with t-PAPS. Gene expression was quantified by qPCR of total leukocyte mRNA. In this case-control study, 102 t-PAPS patients, 17 asymptomatic antiphospholipid (aPL) carriers and 100 controls were evaluated. Increased expression of ANXA3 (P = 0.008) and TNFAIP6 (P = 0.001) and decreased expression of the TXK gene (P = 0.0001) were associated with an increased risk of t-PAPS compared to the control. ANXA3 upregulation was more evident in cases of arterial thrombosis and multiple thrombotic events. There was no difference in the expression of these genes between triple and non-triple aPL positivity. ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression levels were also similar between aPL carriers and controls (P = 0.77; P = 0.48; P = 0.08; P = 0.73, and P = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (ANXA3) and immunity (TNFAIP6, TXK) are dysregulated in t-PAPS compared to controls. Gene dysregulation was not detected in aPL carriers and was not related to the aPL profile, suggesting that this gene signature is related to thrombotic manifestations rather than to aPL burden. Our results suggest that innate immunity and hemostasis pathways are associated with t-PAPS at a molecular level and may play a role in disease severity.

Whole exome sequencing identifies a rare variant in MAS1 gene in a subject with lethal COVID-19

COVID-19 may be considered a multifactorial disease caused by the interaction between the virus itself, as the environmental contribute, and the genetic background of the host. SARS-CoV-2 infection occurs through the interaction between the spike protein and ACE2, a receptor in the host cells. Clinically, COVID-19 is characterized by a high heterogeneity in symptomatology ranging from asymptomatic to severe symptoms, and even worsening to death. This variability relies on the host genomic profile and other individual comorbidities. We performed exome analysis in one family displaying a variable spectrum of SARS-CoV-2 infection despite a common exposure. After segregation analysis, we found that the c.446C>T p.(S149L) in MAS1 gene was exclusively present in the individual with severe COVID-19, who died because of pneumonia and multiple thrombotic events. MAS1 encodes a receptor for Ang1–7 in the renin-angiotensin system (RAS) with an anti-inflammatory, anti-fibrotic and anti-angiogenic effect. We hypothesize that downregulation of RAS, due to this rare variant, might impair the protective effect and concur to the clinical severity of the disease. Our results support the protective role of the ACE2/Ang-(1–7)/Mas1 axis and the potential danger of its dysregulation leading to severe COVID-19 disease; if further confirmed, these findings will be useful for management of critically ill patients.

Rapidly progressing dyspnea and retiform purpura

Rapidly progressing dyspnea and retiform purpura

Rapidly evolving necrotic skin lesions of the face

Rapidly evolving necrotic skin lesions of the face

COVID-19-related thrombotic complications experience before and during delta wave.

ObjectiveHypercoagulability and thrombotic complications seen in SARS-CoV-2 patients, as well as the associated pathophysiology, have been reported extensively. However, there is limited information regarding the factors related to this phenomenon and its association with the COVID-19 delta variant.MethodsA retrospective review including patients admitted to a tertiary center with a COVID-19 positive test and at least one acute thrombotic event confirmed by imaging between June 2020 and August 2021 was performed. We compared the rates of thrombotic events in patients with COVID-19 before and during the Delta peak. We also analyzed the association of the thrombotic complications with demographic characteristics, comorbidities, anticoagulation strategies, and prothrombotic markers while describing other complications secondary to COVID-19 infection.ResultsOut of 964 patients admitted with COVID-19 diagnosis, 26.5% (n=256) had a thrombotic event evidenced by ultrasound (US) or computerized tomography (CT) scan. Venous thromboembolism was found in 60% (n=153), arterial thrombosis in 23% (n=60), and both venous and arterial thromboses in 17% (n=17) of the study cohort. Of all patients, 94% were not vaccinated. Delta variant wave patients (DW) had thrombotic episodes in 34.7% (n=50/144) of cases compared to 25% (n=206/820) of non-Delta wave (NDW) patients, posing an estimated risk 1.36 times higher in patients infected with COVID-19 during the DW than NDW. Overall, DW subjects were significantly younger (p<0.001) with lower BMI (p=0.021) compared to NDW patients. Statistical analyses showed African American patients were more likely to have arterial thrombosis compared to the other groups when testing positive for COVID-19 (OR: 1.78 [CI: 1.04 – 3.05], p=0.035), whereas immunosuppressed patients had less risk of arterial thrombosis (OR: 0.38 [CI: 0.15 – 0.96], p=0.042). Female gender (OR: 2.15 [CI: 1.20 – 3.85]. p=0.009) and patients with active malignancy (OR: 5.99 [CI: 2.14 – 16.78]. p=0.001) had an increased risk of having multiple thrombotic events at different locations secondary to COVID-19.ConclusionCOVID-19 infection is associated with elevated rates of thrombotic complications and an especially higher risk in patients infected during the Delta variant peak. We highlight the importance of vaccination and the development of new anticoagulation strategies for COVID-19 patients with additional hypercoagulable risk factors to prevent thrombotic complications caused by this disease.

Anti-PD-L1 monoclonal antibody for the management of chronic disseminated intravascular coagulation secondary to a urothelial carcinoma: a case report

BackgroundThrombocytopenia is often considered a risk factor for bleeding, but conversely may be associated with an increased thrombotic risk in several clinical situations. Here we present a patient with arterial thrombosis and chronic disseminated intravascular coagulation caused by metastatic urothelial carcinoma. As the treatment for a disseminated intravascular coagulation caused by a neoplasia is the treatment of the underlying disease itself, our case highlights a new therapeutic approach—immunotherapy—in a patient prone to hematological complications due to conventional chemotherapy.Clinical caseA 74-year-old Caucasian male patient with a history of urothelial carcinoma of the bladder and moderate thrombocytopenia had multiple arterial thrombotic events despite antiplatelet therapy and anticoagulation. A diagnosis of chronic disseminated intravascular coagulation in the setting of a metastatic bladder urothelial carcinoma was made. The patient was treated with an anti-PD-L1 monoclonal antibody, and achieved a rapid response with subsequent reversal of the disseminated intravascular coagulation.ConclusionUnexplained arterial or venous thrombosis despite adequate thromboprophylaxis should be investigated, especially in the setting of thrombocytopenia. Chronic disseminated intravascular coagulation is a possible, life-threatening reason for this clinical picture, and should prompt rapid identification of the underlying disease. To the best of our knowledge, this is the second case of chronic disseminated intravascular coagulation due to neoplastic disease treated with immunotherapy.

COVID-19-Related Thrombosis in Japan: Final Report of a Questionnaire-Based Survey in 2020.

A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, and 212 died (3.4%). D-dimer levels were measured in 75.0% of the patients, revealing that 9.2% and 7.6% exhibited D-dimer increases of 3–8-fold and ≥ 8-fold the reference value, respectively. Thrombotic events occurred in 108 patients (1.86% of the 5,807 patients with available data) including symptomatic cerebral infarction in 24, myocardial infarction in 7, deep vein thrombosis in 41, pulmonary thromboembolism in 30, and other thrombotic events in 22. Some patients developed multiple thrombotic events. Thrombosis occurred in 32 patients with mild or moderate COVID-19 severity (0.59% of those with data available) and in 52 patients on ventilation or ECMO (13.5% of severe patients for whom data were available). Thrombosis occurred in 67 patients during worsening clinical condition and in 26 during recovery. Anticoagulant therapy was provided to 893 patients (14.6% of the 6,119 patients with available data), the main reasons being provided as elevated D-dimer levels and worsening clinical condition.

CATASTROPHIC THROMBOTIC STORM IN A YOUNG HISPANIC FEMALE DIAGNOSED WITH DEEP VEIN THROMBOSIS

Thrombotic storm (TS) is a rare and lethal condition characterized by multiple thrombotic events involving both venous and arterial circulation. Its rapid onset and aggressive nature represent a critical challenge upon initial medical encounter. A 37-year-old Hispanic female presented with a cast

Thrombotic storm and malignancy in elderly woman: a case report

Thrombotic storm is a state of hypercoagulability of relevance in the context of neoplasias, trauma, gestation, autoimmune diseases and deficiencies of coagulation proteins. The following case brings this topic associated with weight loss and a subsequent atypical primary site of neoplasm found in postmortem biopsy. Objectives: To present an atypical case of thrombosis in several sites in elderly women in a context of consumptive syndrome without definite primary cancer site; to discuss differentials and pathophysiological processes relevant to the case. Case report: A 74-year-old female patient, previously healthy, presented a constipation associated with weakness in right superior limb, edema and weakness of left lower limb, with difficulty in gait and subsequent bed restriction. It evolved with multiple thrombotic events (axillary arterial, segmental branches of the left pulmonary artery, hepatic, renal and splenic parenchymal infarction, deep venous thrombosis in the common femoral vein, superficial femoral vein and left femoral vein, and right superficial femoral vein thrombosis). Abdominal computed tomography (CT) showed hepatic nodules suggestive of metastases and lymph node enlargement up to 2.0 cm. Hepatic biopsy was performed by interventional radiology resulting inconclusive due to extensive areas of necrosis. Laboratory tests revealed hepatic enzymes, canalicular and direct bilirubin with increased and increasing values, normochromic normocytic anemia worsening and with increasing values of RDW and platelets. Ca19.9 accounted for &gt; 1,000 U / mL. FAN, anticardiolipin IgM and IgG, lupus anticoagulant, ANCA negative. Death verified 12 days after admission, despite intensive care. Necroscopic report showed adenocarcinoma centered in bile ducts involving gallbladder and extra and intrahepatic bile ducts with vascular dissemination (pulmonary and lymph node metastases) and extension to gastric wall and small intestine. Post-mortem diagnosis of cholangiocarcinoma was performed. Discussion: the case discusses is of multiple thrombotic events in unusual sites associated with non-specific findings at the beginning. The hypothesis of phospholipid antibody syndrome (APS) was proposed although it is unlikely in an elderly patient. Subsequent evaluation for thrombophilias was not done since weight loss and abdominal CT with multiple hepatic nodules suggested neoplasia of indeterminate site. Hence, SAF was discarded and the patient died without diagnosis of primary site due to the difficulty of the case. Conclusion: neoplasia of uncommon sites can be a disease of hard diagnosis and management especially in patients worsening in a short time. However they must be considered with proper investigation in patients with multiple thrombotic events due to the very known association with these findings.

STEMI and CVA in Hypercoagulable State with Ostium Secundum Defect.

Atrial septal defect (ASD) is a risk factor for multiple vascular thrombotic events, which can occur either sequentially or simultaneously. In this report we present a case of ST-elevation myocardial infarction (STEMI) and cerebrovascular accident (CVA). The severity of adverse cardiovascular or cerebrovascular events can be increased by the presence of specific type of ASD, such as a patent foramen ovale (PFO) or osteum secundum defect. This case report discusses a unique presentation of a 48-year old male on warfarin therapy for a history of cerebral venous thrombosis (CVT) who subsequently presented with simultaneous STEMI with CVA, and who was incidentally found to have an ostium secundum defect on echocardiography. He was emergently taken for cardiac catheterization, which revealed significant proximal LAD occlusion. There has been a long standing debate within the international scientific communities regarding the therapeutic benefit of PFO closure for long-term secondary prevention of recurrence CVA. We discuss the different points of view regarding PFO closure for secondary prevention of CVA with a review of the literature on this rather controversial topic.

Addison's disease in antiphospholipid syndrome: a rare complication.

SummaryAddison’s disease (AD) is the most common endocrine manifestation of antiphospholipid syndrome (APS), but it remains a very rare complication of the syndrome. It is caused by adrenal venous thrombosis and consequent hemorrhagic infarction or by spontaneous (without thrombosis) adrenal hemorrhage, usually occurring after surgery or anticoagulant therapy. We present a clinical case of a 36-year-old female patient with a previous diagnosis of APS. She presented with multiple thrombotic events, including spontaneous abortions. During evaluation by the third episode of abortion, a CT imaging revealed an adrenal hematoma, but the patient was discharged without further investigation. A few weeks later, she presented in the emergency department with manifestations suggestive of adrenal insufficiency. Based on that assumption, she started therapy with glucocorticoids, with significant clinical improvement. After stabilization, additional investigation confirmed AD and excluded other etiologies; she also started mineralocorticoid replacement. This case illustrates a rare complication of APS that, if misdiagnosed, may be life threatening. A high index of suspicion is necessary for its diagnosis, and prompt treatment is crucial to reduce the morbidity and mortality potentially associated.Learning points:AD is a rare but life-threatening complication of APS.It is important to look for AD in patients with APS and a suggestive clinical scenario.APS must be excluded in patients with primary adrenal insufficiency and adrenal imaging revealing thrombosis/hemorrhage.Glucocorticoid therapy should be promptly initiated when AD is suspected.Mineralocorticoid replacement must be started when there is confirmed aldosterone deficiency.Hypertension is a common feature of APS; in patients with APS and AD, replacement therapy with glucocorticoids and mineralocorticoids may jeopardize hypertension management.

Premature Myocardial Infarction as the Presenting Sign of Hypercoagulable Syndrome

Introduction Premature myocardial infarction (MI) in a young patient proves to be a challenge to manage. In the absence of family history or provoking factors, etiology can be difficult to determine. Hypercoagulable syndromes should be considered as an etiology for premature MI, as future management may be influenced by the presence of these syndromes. We report the case of a young heart-kidney transplant recipient presenting with multiple thrombotic events including premature MI, LVAD thrombosis, and deep vein thrombosis (DVT) in the setting of May-Thurner Syndrome (MTS) exemplifying the importance of thorough hypercoagulability testing. Case Report Our patient is a 41-year-old male with a history of MI at age 37, resulting in ischemic cardiomyopathy complicated by cardiogenic shock requiring LVAD placement for bridge to transplant. Patient's post LVAD course was complicated by recurrent LVAD thrombosis despite adequate anticoagulation (AC) requiring two device exchanges. Hypercoagulability testing was limited due to the necessity of chronic AC. One month after undergoing heart-kidney transplant, patient presented with left lower extremity (LLE) pain and difficulty ambulating with duplex ultrasound showing DVT of LLE extending from the L common iliac vein to the L popliteal vein, requiring thrombectomy. Venography identified narrowing of the L common iliac vein confirming the diagnosis of MTS and an iliac vein stent was placed. Repeat hypercoagulability testing revealed an elevated factor VIII (FVIII) activity level to 319% of normal, warranting long-term AC with an elevated therapeutic INR range and high dose aspirin. Patient has had no recurrent thrombosis since starting this regimen. Summary Patients with multiple thrombotic events should undergo thorough hypercoagulability testing to identify risk for future thromboses and need for AC. Traditionally, elevated FVIII levels are thought to be an acute phase reactant, not necessitating AC. However, it has recently been shown that patients with an elevated FVIII level are at significant risk for thrombosis and require long-term AC. Our case highlights the importance of early FVIII level testing in hypercoagulability evaluation.

A Battle against the Odds: Intensive Therapy in Thrombotic Storm

Thrombotic storm (TS) is a rare life-threatening entity that is characterized by multiple thrombotic events affecting diverse vascular sites occurring over a short period of time (days to weeks). We describe a case of a young boy who developed extensive and rapidly progressive thrombosis which required intensive treatment that included the use of triple antithrombotic therapy, pharmacomechanical thrombectomy, systemic thrombolytic therapy, and the combined use of plasmapheresis and immunosuppression.

Phlegmasia cerulea dolens and multiple recurrent thrombotic events as the presenting feature of EML4-ALK translocated non-small cell lung cancer

Abstract Phlegmasia cerulea dolens (PCD) is a rare presentation of deep vein thrombosis (DVT) which clinically mimicks arterial ischemia and is caused by extensive thrombotic occlusion of the venous outflow of a major vein of an extremity. DVT is a common and potentially life-threatening complication in patients with lung cancer. We report the case of a patient who developed PCD in an upper limb while receiving anticoagulation treatment with low-molecular-weight heparin (LMWH) for recurrent venous thromboembolism (VTE) events at presentation of EML4-ALK translocated metastasic lung adenocarcinoma. Crizotinib therapy was associated not only with response of metastatic lesions but with a dramatic improvement of cancer-associated hypercoagulability. To our knowledge, this is the first case reporting PCD in an ALK-rearranged advanced NSCLC patient.

How I treat catastrophic thrombotic syndromes

AbstractCatastrophic thrombotic syndromes are characterized by rapid onset of multiple thromboembolic occlusions affecting diverse vascular beds. Patients may have multiple events on presentation, or develop them rapidly over days to weeks. Several disorders can present with this extreme clinical phenotype, including catastrophic antiphospholipid syndrome (APS), atypical presentations of thrombotic thrombocytopenic purpura (TTP) or heparin-induced thrombocytopenia (HIT), and Trousseau syndrome, but some patients present with multiple thrombotic events in the absence of associated prothrombotic disorders. Diagnostic workup must rapidly determine which, if any, of these syndromes are present because therapeutic management is driven by the underlying disorder. With the exception of atypical presentations of TTP, which are treated with plasma exchange, anticoagulation is the most important therapeutic intervention in these patients. Effective anticoagulation may require laboratory confirmation with anti–factor Xa levels in patients treated with heparin, especially if the baseline (pretreatment) activated partial thromboplastin time is prolonged. Patients with catastrophic APS also benefit from immunosuppressive therapy and/or plasma exchange, whereas patients with HIT need an alternative anticoagulant to replace heparin. Progressive thrombotic events despite therapeutic anticoagulation may necessitate an alternative therapeutic strategy. If the thrombotic process can be controlled, these patients can recover, but indefinite anticoagulant therapy may be appropriate to prevent recurrent events.