Spontaneous coronary artery dissection in a young patient with antiphospholipid syndrome.

A 28-year-old man diagnosed with triple positive antiphospholipid syndrome (APS) and undergoing warfarin experienced three separate admissions to the cardiac ward within a one-month period due to escalating chest pain. While the initial two admissions revealed normal results in cardiological investigations, such as blood tests, electrocardiogram, and echocardiography, the third admission unveiled signs of ST-elevation myocardial infarction (STEMI), despite the patient maintaining an INR (International Normalized Ratio) of 4. Subsequent percutaneous coronary intervention (PCI) exposed spontaneous coronary artery dissection (SCAD) of type 3. Faced with hemodynamic instability and worsening symptoms, the patient underwent stenting and was prescribed dual antiplatelet therapy in addition to warfarin. A follow-up evaluation one month later indicated a normalization of his condition.

Incidence of venous thromboembolism, recurrence, and bleeding after isolated superficial vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital.

BACKGROUND: There are limited data on the long-term risk of venous thromboembolism (VTE) after high-risk isolated superficial vein thrombosis (iSVT) treated with anticoagulants. OBJECTIVES: To determine the short- and long-term risk of VTE and iSVT recurrence after cessation of anticoagulant treatment and to calculate 45-day cumulative bleeding incidence in patients with iSVT. METHODS: Between January 2014 and December 2021, 229 patients with high-risk iSVT (ie, thrombus length ≥5cm), without active cancer, with no history of VTE or iSVT, and who had received anticoagulant treatment for the iSVT were identified through the Venous Thrombosis Registry in Østfold Hospital (TROLL registry), Norway. Cumulative incidences of VTE and iSVT recurrence, as well as cumulative incidences of major and clinically relevant nonmajor bleeding events, were assessed. RESULTS: Median age was 60 years (IQR, 48-71), and 125 (55%) were women. Most patients were treated with direct oral anticoagulants (74%), and of these, 79% received a dose of rivaroxaban 10 mg daily. Low-molecular-weight heparin was given to 26% of the patients. The 1- and 5-year cumulative incidences of VTE after iSVT were 4.6% (95% CI, 2.5-8.3) and 15.9% (95% CI, 10.8-22.9), respectively. Further, the 1- and 5-year cumulative incidences of iSVT recurrence were 6.5% (95% CI, 3.9-10.7) and 15.9% (95% CI, 10.8-23.1), respectively. The overall 45-day cumulative incidence of major and clinically relevant nonmajor bleeding events was 0.4% (95% CI, 0.06-3.06) and 1.8% (95% CI, 0.7-4.6), respectively. No major bleeding events were observed in patients treated with direct oral anticoagulants. CONCLUSION: Despite anticoagulant treatment, the risk of VTE after high-risk iSVT was substantial, while bleeding complications were low.

A woman in her fifties with cirrhosis of the liver and postural dyspnoea. / En kvinne i 50-årene med levercirrhose og stillingsavhengig dyspné.

A woman in her fifties with advanced cirrhosis of the liver was admitted multiple times with recurrent pleural effusion and ascites. She was accepted for liver transplantation, at which time she developed postural dyspnoea and a drop in oxygen saturation.

Incidence of bleeding and recurrence in isolated distal deep vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital.

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is a common presentation of deep vein thrombosis. There are limited data on the long-term risk of recurrence after IDDVT. OBJECTIVES: We aimed to determine the short- and long-term incidence of venous thrombosis (VTE) recurrence after cessation of anticoagulation and the 3-month incidence of bleeding during anticoagulant treatment in patients with IDDVT. METHODS: Between January 2005 and May 2020, 475 patients with IDDVT and without active cancer were identified from the Venous Thrombosis Registry in Østfold Hospital, which is an ongoing registry of consecutive patients with VTE at Østfold Hospital, Norway. Major and clinically relevant, nonmajor bleeding as well as recurrent VTE were registered, and the cumulative incidences of these events were assessed. RESULTS: The median age of the patients was 59 years (IQR, 48-72 years), 243 (51%) patients were women, and 175 events (36.8%) were classified as unprovoked. The 1-, 5-, and 10-year cumulative incidences of recurrent VTE were 5.6% (95% CI, 3.7-8.4), 14.7% (95% CI, 11.1-19.4), and 27.2% (95% CI, 21.1-34.5), respectively. The recurrence rates were higher for unprovoked IDDVT than for provoked IDDVT. Among the recurrent events, 18 (29%) were pulmonary embolisms and 21 (33%) were proximal deep vein thromboses. The 3-month cumulative incidence of major bleeding was 1.5% (95% CI, 0.7-3.1) overall and 0.8% (95% CI, 0.2-3.1) when restricted to patients treated with direct oral anticoagulants. CONCLUSION: Despite initial treatment, the long-term risk of VTE recurrence after first-time IDDVT is high. The bleeding rates during anticoagulation, particularly with direct oral anticoagulants, were acceptably low.

A pregnant woman in her thirties with abdominal pain, seizures and haemorrhagic shock. / En gravid kvinne i 30-årene med magesmerter, kramper og blødningssjokk.

A pregnant woman at term was admitted to the emergency department with abdominal pain, generalised seizures and haemorrhagic shock. An outpatient check-up five days earlier showed good general condition, normal blood pressure and normal fetal heartbeat.

SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people.

Background: SARS-CoV-2 adenoviral vector DNA vaccines have been linked to the rare but serious thrombotic postvaccine complication vaccine-induced immune thrombotic thrombocytopenia. This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 health care personnel; 521 were recruited after the first dose of adenoviral vector ChAdOx1-S (Vaxzevria, AstraZeneca) vaccine and 46 were recruited prospectively before vaccination with a messenger RNA (mRNA) vaccine, either Spikevax (Moderna, n = 38) or Comirnaty (Pfizer-BioNTech, n = 8). In the mRNA group, samples were acquired before and 1 to 2 weeks after vaccination. In addition to the prevaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer levels, and free tissue factor pathway inhibitor (TFPI) levels were analyzed. Results: No participant experienced thrombosis, vaccine-induced immune thrombotic thrombocytopenia, or thrombocytopenia (platelet count <100 × 109/L) 1 week to 1 month postvaccination. There was no increase in thrombin generation, D-dimer level, or TFPI level in the ChAdOx1-S vaccine group compared with controls or after the mRNA vaccines compared with baseline values. Eleven of 513 (2.1%) participants vaccinated with ChAdOx1-S had anti-PF4/polyanion antibodies without a concomitant increase in thrombin generation. Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer levels, or TFPI levels compared with baseline or unvaccinated controls. These findings argue against the subclinical activation of coagulation post-COVID-19 vaccination.

The venous thrombosis registry in Østfold Hospital (TROLL registry) - design and cohort description.

Purpose: The incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real-world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry Population: The Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow-up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits. Findings to Date: From January 2005 to June 2021, 5037 patients were eligible for research in TROLL. Median age was 67 years (interquartile range, 55-77), and 2622 (52.1%) were male. Of these, 2736 (54.3%) had pulmonary embolism (PE), 2034 (40.4%) had deep vein thrombosis (DVT), and 265 (5.3%) had upper-extremity DVT or splanchnic or cerebral sinus vein thrombosis. In total, 2330 (46.3%) were classified as unprovoked VTE, and 1131 (22.5%) had cancer. Direct oral anticoagulants were the most frequent therapeutic agents (39.3%) followed by low-molecular-weight heparins (30.4%) and vitamin K antagonists (30.3%). Outpatient treatment for PE increased from 4% in 2005 to 23% in 2019. Future Plans: TROLL is a population-based ongoing registry that represents a valuable source of real-world data that will be used for future research on the management and outcomes of VTE.

Successful Control of Hepatitis B Virus Reactivation following Restart of Ibrutinib in Chronic Lymphocytic Leukaemia.

Ibrutinib is a targeted therapy drug that blocks the activity of Bruton's tyrosine kinase, and it is an approved treatment for several mature B-cell malignancies including chronic lymphocytic leukaemia (CLL). Side effects include infections, cytopenia, nausea, and diarrhoea. In this report, we describe a case of hepatitis B reactivation in a female CLL patient undergoing treatment with ibrutinib. Diagnosis was confirmed with highly elevated hepatitis B virus DNA and a prior blood sample confirmed previous exposure. Ibrutinib was paused, and antiviral therapy was initiated with prompt clinical improvement. Ibrutinib was reinitiated shortly after clinical improvement. Thus, our case report demonstrates that systematic HBV screening is essential before starting treatment with ibrutinib. We suggest that antiviral prophylaxis is considered for patients at risk of reactivation, and ibrutinib may be continued following HBV reactivation with proper antiviral treatment.

Subacute thyroiditis after COVID-19. / Subakutt tyreoiditt etter covid-19.

BACKGROUND: Since the beginning of the pandemic we have learned much about acute organ complications due to COVID-19, but we are still only beginning to understand the post-infection complications. CASE PRESENTATION: A man in his forties was diagnosed with subacute thyroiditis after a mild COVID-19 infection. This is an important differential diagnosis to consider if after a period of improvement, an infected patient develops fever, pain around the region of the thyroid (throat/neck) and/or symptoms of hyperthyroidism. INTERPRETATION: Subacute thyroiditis is thought to be initiated by a viral infection or postviral inflammatory process, often in patients with a history of an upper respiratory infection typically two to eight weeks prior to the onset of thyroiditis. The condition is believed to be triggered by an antigen created by the virus. Subacute thyroiditis must be on the list of possible differential diagnoses in patients with COVID-19 whose condition deteriorates after a period of improvement.

An observational study to identify the prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in Norwegian health care workers after COVID-19 vaccination.

BACKGROUND: The COVID-19 vaccine from AstraZeneca (AZD1222) is one of several vaccines introduced to provide immunity against SARS-CoV-2. Recently, more than 50 cases have been reported presenting a combination of thrombosis, thrombocytopenia, and remarkably high levels of anti-platelet factor 4 (PF4)/polyanion antibodies post-AZD1222 vaccination. Now linked to the vaccine, the condition is referred to as vaccine-induced immune thrombotic thrombocytopenia. The European Medicines Agency still recommends vaccination with AZD1222, but several European countries have temporally paused and/or restricted its use because of the perceived risk of this severe side effect. Because there is no description of PF4/polyanion antibody testing in the clinical trials, knowledge about the prevalence of such antibodies in a vaccinated cohort is needed. OBJECTIVES: To investigate prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in a population recently vaccinated with AZD1222. PATIENTS/METHODS: Four hundred and ninety-two health care workers recently vaccinated with the first dose of AZD1222 were recruited from two hospitals in Norway. Study individuals were screened for thrombocytopenia and the presence of anti-PF4/polyanion antibodies with a PF4/PVS immunoassay. Side effects after vaccination were registered. RESULTS: The majority of study participants had normal platelet counts and negative immunoassay. Anti-PF4/polyanion antibodies without platelet activating properties were only detected in six individuals (optical density ≥0.4, range 0.58-1.16), all with normal platelet counts. No subjects had severe thrombocytopenia. CONCLUSIONS: We found low prevalence of both thrombocytopenia and antibodies to PF4/polyanion-complexes among Norwegian health care workers after vaccination with AZD1222.

Seventy patients treated for COVID-19 by Østfold Hospital Trust. / 70 pasienter med covid-19 innlagt ved Sykehuset Østfold.

BACKGROUND: There is a need for further data on the COVID-19 situation in Norway. Our aim was to describe the patients admitted to our local hospital with COVID-19 in the spring of 2020. MATERIAL AND METHOD: Data were retrieved retrospectively from our local quality register for COVID-19 and include all patients admitted to Østfold Hospital in the period 10 March 2020-31 May 2020. RESULTS: A total of 70 patients were admitted, of whom 47 (67 %) were men. The mean age was 59 years (range 18-95). The most common comorbid conditions were obesity (n = 22, 31 %), chronic coronary artery disease (n = 21, 30 %) and diabetes (n = 17, 24 %). Thirteen patients (19 %) had no comorbidities. The most common symptoms were cough (n = 56, 80 %), dyspnoea (n = 51, 73 %) and fever (n = 48, 69 %). The most frequent complications were cardiac manifestations (n = 18, 26 %), acute respiratory distress syndrome (n = 14, 20 %) and acute kidney injury (n = 9, 13 %). Four (6 %) patients developed venous thromboembolism. Twenty patients (29 %) became critically ill. Thirteen (19 %) received treatment in the intensive care unit, and seven (10 %) died while in hospital. INTERPRETATION: Most of those admitted were middle-aged men. Many had no comorbidities. The most frequent non-respiratory complications were cardiac manifestations and kidney injury. A large proportion of patients became critically ill secondary to acute respiratory distress syndrome.

Transformation to plasmablastic lymphoma in CLL upon ibrutinib treatment.

Chronic lymphatic leukaemia (CLL) is the most common leukaemia in the Western world. Ibrutinib, a tyrosine kinase inhibitor, is the treatment of choice on relapse or p53-dysfunction. Richter's transformation to diffuse large B cell lymphoma is most often seen. However, transformation to other aggressive lymphomas as plasmablastic lymphoma (PBL) does occur. PBL is an extremely aggressive lymphoma and is usually treated using a CHOP-like regimen (cyclophosphamide, doxorubicin, vincristine and prednisone/dexamethasone), but with poor outcome. The only curative treatment is allogeneic stem cell transplant (ASCT).We report on a case of CLL treated with ibrutinib that underwent transformation to PBL. Due to high expression of CD138, we added daratumumab to the chemotherapy with a good, but transitory response. The case did not make it to an ASCT. Targeting CD138 by daratumumab may be added to chemoimmune therapy for PBL.

Cold agglutinin disease revisited: a multinational, observational study of 232 patients.

We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate fourfold differences between cold and warmer climates regarding prevalence (20 vs 5 cases/million) and incidence (1.9 vs 0.48 cases/million per year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin <8 g/dL. Identification of typical features of CAD-associated lymphoproliferative disorder in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work includes a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift toward deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.

Long-term outcomes of patients treated with rituximab as second-line treatment for adult immune thrombocytopenia - Follow-up of the RITP study.

RITP was a double-blind randomized, 78-week follow-up trial in which 109 adults with immune thrombocytopenias (ITP) who failed to achieve adequate response to steroids, were randomized to receive rituximab or placebo. Here, we provide the duration of response, splenectomy and mortality rates based on extended follow-up after completion of the RITP study. Extended follow-up data were retrospectively collected for 72 (83%) patients out of the 84 patients who were not splenectomized during the initial RITP study. For the present analysis, median [interquartile range] duration of follow-up after randomization was 72 [62-82] months. Median duration of response among patients who achieved an initial response was significantly longer in patients who received rituximab (8·2 [5·5-16·7] months) as compared to placebo (1·8 [1·3-3·6] months), P = 0·036. Overall, 35 patients underwent splenectomy (13 in the rituximab, and 22 in the placebo arm, P = 0·12). Eleven patients (10%) died during the study: five in the rituximab and six in the placebo arms, including four deaths from severe bleeding. Although most rituximab-treated patients eventually relapsed, a longer duration of response and a trend towards lower splenectomy rate were observed in rituximab-treated patients.

Envenomation by the common European adder (Vipera berus): a case series of 219 patients.

OBJECTIVES: Every year, several patients are bitten by the common European adder (Vipera berus). The aim of this study is to present a large consecutive case series of patients bitten by V. berus, and to identify signs and symptoms indicative of complicated illness. PATIENTS AND METHODS: This is a retrospective case series from the Hospital of South West Jutland, Denmark. All 219 patients bitten by V. berus (diagnosed by history or clinical findings) from 1994 to 2012 were identified through hospital databases. A severity grading from 1 to 5 was applied, and epidemiology, symptoms and signs, complications, treatment and laboratory data were extracted from the hospital databases. RESULTS: The most common complaints on admission were pain, nausea, abdominal pain, diarrhoea and dizziness, with discoloration and oedema being the most common symptoms. Few patients experienced syncope, palpitations or respiratory distress. Fifteen percent of all patients were transferred to the ICU and 2% (all children) were suspected of having compartment syndrome. Leucocytosis, gastrointestinal symptoms and hypotension were risk factors for complicated disease. CONCLUSION: Most patients only showed symptoms of no or mild envenomation. Fifteen percent were transferred to the ICU and five patients (all children) required fasciotomy because of suspected compartment syndrome. Only 10 patients received antivenom.

Prophylactic use of eculizumab during surgery in chronic cold agglutinin disease.

Primary chronic cold agglutinin disease (CAD) is an autoimmune haemolytic anaemia in which a specific bone marrow lymphoproliferative disorder causes production of cold agglutinins (CA). Binding of CA to erythrocyte surface antigens results in a predominantly extravascular haemolysis that is entirely complement dependent. Because of complement activation, exacerbations are common during febrile infections, trauma or major surgery. Involvement of the terminal complement pathway with C5-mediated intravascular haemolysis is probably not prominent in stable disease but is supposed to be of importance in exacerbations following acute phase reaction.We report on a patient with CAD prone to exacerbation of haemolysis during acute phase reactions who was scheduled for cardiac surgery. To prevent her having an exacerbation of haemolysis, we chose to treat her prophylactically with eculizumab along with the usual perioperative precautions. Aortic valve replacement was undertaken with full cardiopulmonary bypass at normothermia. The procedure was successful; no exacerbation of haemolysis was observed, and transfusion requirements did not exceed what could be expected.