[ ISSN : 2573-3680 ]
Thrombocytopenia; Heparin-treatment; Anticoagulation therapies; NOACs
This case report illustrates a patient with Heparin-Induced Thrombocytopenia (HIT) who was successfully treated with Apixaban. HIT is an adverse drug reaction induced by treatment with heparin. The optimal anticoagulation strategy remains uncertain. This case presents a patient who developed massive pulmonary embolisms post total knee replacement, she was then treated with low-molecular-weight heparin (LMWH), which lead to bleeding and a critically platelet count drop, indicating serious HIT 2 syndrome. By discontinuation of LMWH and switch to Apixaban in a modified dose regime, we managed to stop the life-threatening complications of LMWH. The platelet count recovered, and the patient survived.
Heparin-Induced Thrombocytopenia (HIT) is an adverse drug reaction induced by treatment with heparin, which occurs more likely with unfractionated heparin (UFH) than with low-molecularweight heparin (LMWH) [1]. HIT has been categorized into two groups; HIT type 1 is defined as a mild reaction, non-immune mediated. No complications are seen, and the thrombocytopenia will show spontaneous remission whilst continued treatment with heparin. HIT type 2 is an immunemediated reaction [2]. Usually, the platelet 4 factor (PF4) is stored in and released from the alpha granules of activated platelets. PF4 binds to heparin due to high affinity, and this might trigger the formation of immunoglobulin G (IgG) antibodies.
HIT occurs only if IgG is attached to the heparin-PF4 complex and this binds to platelet receptors. This leads to both a critical prothrombotic situation and bleedings caused by thrombocytopenia [3,4]. Type 2 HIT usually inserts 5-14 days after the first dose of heparin. However, one single dose of heparin may cause the development of antibodies, and re-exposure to heparin within 3 months may cause serious life-threatening reactions [5,6]. Platelet count <150×109 /L defines thrombocytopenia, while severe thrombocytopenia is defined by count <50×109 /L. Consequences can be life-threatening with a very high mortality rate (30%) [7,8], caused by bleedings (thrombocytopenia) and a hypercoagulable state, where most patients developed severe thromboembolic complications. Today there are no evidence-based recommendations how to treat these patients [9].
The new oral anticoagulants (NOACs) have shown relevant properties for the management of HIT, by rapid onset of action, oral administration, ease of use and lack of monitoring [10].
A 67-year-old white female patient presented to emergency department with dehydration and a medical history of a right total knee arthroplasty 8 days before arrival. No clear symptoms other than loss of appetite. The patient was hemodynamically stable, which included normal blood pressure and pulse. Routine admission laboratory for general medical patients showed increased C-Reactive Protein (CRP) level at 190 mg/L [<10 mg/L] and a low haemoglobin level at 5.4 mmol/L [7,3 - 9,5 mmol/L].
She started treatment with 4 g piperacillin combined with 0.5 g tazobactam on the suspicion of pneumonia. Due to the high risk of developing thrombosis by being bedridden and the suspicion of pulmonary embolism, the patient was treated with Dalteparin 200IU/kg of body weight (Figure 1).
Figure 1: The trend of thrombocytopenia in the patient.
Computed Tomography (CT) scan of the chest verifies bilateral infiltrates and pulmonary embolism was disconfirmed, so the patient was treated for pneumonia with intravenous 4 g Piperacillin combined with 0.5 g Tazobactam in 11 days and 500 mg Clarithromycin in 7 days, and then discharged from the hospital. 5 days later the patient developed dyspnea, and due to d-dimer 20 L [<0.7] (Table 1) and chest CT verified bilateral massive pulmonary embolisms, treatment with Dalteparin 200IU/kg of body weight was immediately effectuated (Figure 1). Ultrasound of lower extremities and the pelvis were without thromboses.
Table 1: Laboratory test results after heparin exposure.
12 hours later we observed gingival bleeding, petechiae on lower extremities and ecchymoses on the truncus. Platelet count showed a decrease of 88.9% (from 170×109 /L to 20×109 /L). Dalteparin was then immediately discontinued and due to bleeding and thrombocytopenia transfusion of platelet concentrate was given, which aggravate the patient’s situation. As a result of more bleeding and periphery embolies, we observed a further drop in platelet count (16×109 /L). As blood test analysis for antibodies directed against PF4 was not locally available, the diagnosis of HIT 2 was based on the available blood tests (Table 1) and the 4T score (Table 2).
Table 2: 4Ts Score of the patient
To verify the diagnosis, a blood test was later taken and sent abroad, but unfortunately it went missing. At this point, the patient was in a life-threatening situation with bleedings caused by thrombocytopenia and with severe thromboembolic complications caused by a hypercoagulable state. To turn this situation, we started with a single dose of Apixaban 2.5mg. We then observed increasing platelet count, and thereafter a modified regime was used to treat the patient, that consisted of Apixaban 2.5 mg BID, then Apixaban 5.0 mg BID and then a treatment dose of Apixaban 10.0 mg BID 1 week. During the next 7 days, the platelet count increased to 190×109 /L, and the patient was asymptomatic. Figure 1 illustrates the increase in platelets during Apixaban treatment, in the same period we observed a decrease in fibrinogen and APTT and d-dimer (Table 1). 4Ts score was used to investigate if the patient were likely to have HIT, by assessing the probability of having HIT. Score result >4 represents a high probability of HIT and can be divided into intermediate and high risk. The variables include thrombocytopenia, timing, thrombosis and the likelihood of another diagnosis. In our case, the patient scored 7 points (Table 1), as a result of the decrease in platelet count of 89%, timing <4 days after exposure, bilateral PE and no other obvious reasons.
2 points were given if the patient had a >50% platelet count decrease, decrease in 5-10 days, proven new thrombosis and no other explanation for platelet count decrease. 1 point was given if the patient had a 30-50% platelet count decrease, consistent with 5-10 days/decrease <1 day with lately heparin exposure, progressive/ recurrent thrombosis and possibly no other evident cause. Lastly, 1 point was given, if the patient had <30 % platelet count decrease, a decrease in less than 5 days (with no recent heparin exposure), none thrombosis nor other present cause [11].
HIT can occur in 5% of patients exposed to heparin, it is an extremely severe condition with a high mortality rate. Usually, HIT occurs in patients treated with UFH; however, in this case report the patient was exposed to LMWH. Interestingly in this case, the patient before developing pulmonary embolism was treated with one single dose of LMWH due to the high risk of developing thrombosis by being bedridden and suspicion of pulmonary embolism. Subsequently, the platelet count actually increases from 251×109 /L to 423×109 /L.
This single dose of LMWH might have caused the development of antibodies that remained in the patient and caused both the extreme hypercoagulable state and the extreme drop in platelets (20×109 /L) when the patient shortly after was exposed to heparin due to life-threatening pulmonary embolism. Whether the pulmonary embolism was due to the already existing antibodies which caused a prothrombotic state remains unclear.
But consequently, just a few hours after retreatment with heparin 28/2 due to massive pulmonary embolisms, the patient developed a life-threatening thrombocytopenia and a prothrombotic state which in this case lead to a severe health state with pulmonary and periphery embolisms, which usually ends fatally in 30% of the patients. There are no existing guidelines on how to manage this critical condition, to our knowledge, and only a few case reports have previously been published. In our case we successfully used a modified regime that consisted of Apixaban 2.5 mg BID for 1 day, then Apixaban 5.0 mg BID and then a treatment dose of Apixaban 10.0 mg BID for 1 week in order to restore the haemostatic balance.
Treatment of HIT mainly consists in discontinuing heparin treatment and switching to an alternative anticoagulant, which could be direct thrombin inhibitors or direct factor, Xa inhibitors. Treatment with warfarin and thrombocyte transfusions is contraindicated as the risk of thrombosis increases [9]. Apixaban was used in this case for anticoagulation management as the HIT antibodies do not target the drug [12]. This treatment regime is supported by a few other case reports in which describes the beneficial effect of NOACs in the treatment of HIT syndrome [13,14].
Heparin treatment among others has potential to induce thrombocytopenia in patients. This case report suggests attention to platelet counts in patients treated with LMWH as well as a careful clinical examination of the patient can be crucial for the best prognosis. In this case, the patient is treated first with one single dose of LMWH as prophylaxis, and then gets exposed with LMWH again due to pulmonary embolism, which causes the development of a fulminant immune-mediated HIT reaction. Our patient had an extensive clot burden and a critical platelet drop.
Data in treatment of these patients are very limited. However, our modified treatment with Apixaban, we managed to turn this fierce reaction and critical situation, and the recovered patient is now dismissed from the hospital with a continued treatment with Apixaban 5 mg BID for at least 6 months. This case enlightens the need for a worldwide data collection for this type of patient in order to make international treatment guidelines for HIT 2 patients. This case report demonstrates that Apixaban can be used as a safe treatment option in patients with HIT.
Patient consent: A signed informed consent was obtained from the patient before writing the case report. Author Contributions: All authors contributed to analysis and interpretation of the data. All authors contribute to drafting, critical revision and final approval of the article. Conflicts of Interest: The authors received support from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, MSD Denmark ApS and Bayer. The sponsors had no role in data collection, data interpretation or the writing of this publication.
Bhardwaj P, Petersen JR and Fornitz GG. The Beneficial Effect of Apixaban in the Treatment of Heparin-Induced Thrombocytopenia (HIT 2). SM J Clin Med. 2018; 4(2): 1034.
The purpose of this statement is none other than to highlight the importance of ethical standards and quality required in basic and applied research currently being done so we can subsequently inform health care professionals of new developments that are taking place in this area.
Ma. Esperanza Rodríguez-van Lier*
Chemotherapy is commonly used in cancer treatment. So far, chemotherapy agents can be categorized into three types: classical chemotherapeutic drugs, molecular target agents and cellular machineries target drugs.
Ziyou Wang1,2 and Zunnan Huang1,2*
Blood transfusion can cause some transfusion adverse reactions. In order to understand the incidence of adverse transfusion reactions, we performed a meta-analysis in Chinese hospitals. Of 809 literatures, seven studies involving a total of 211, 050 patients with blood transfusion treatment were included in this meta-analysis. Meta-analysis showed that the total incidence of adverse reactions was 0.4% [95% CI (0.2, 0.9), P < 0.0001]. Further subgroup analysis showed that the incidence of febrile and allergic reactions was 0.2% [95% CI (0.1, 0.5), P < 0.0001] and 0.2% [95% CI (0.1, 0.3), P < 0.0001], respectively. The common blood components caused adverse reactions were red blood cell, plasama, and platelet in clinical practice.
Yulu Gao1 , Qinyun Li2 , Zongshuai Gao2 , Yunxia Zhu4 , Yanqiu Liao5 , Changtai Zhu2 *# , Yongning Sun3 *#
Background: CT scanning remains one of the most routinely used diagnostic tools in a setting of Interstitial Lung Disease (ILD). New and improved technologies, such as High Resolution Computer Tomography (HRCT) have revolutionized the quality of imaging, leading to a prominent increase in number of incidental findings that may or may not be of any clinical significance. The aim of this study was to evaluate the prevalence of incidental findings on thoracic CT and their clinical significance.
Methods: Retrospective analysis was conducted on a cohort of 84 patients referred to our academic center as cases of ILD. Patients were referred for further evaluation between January 2000 and January 2014 and were followed over the disease course. CT scans were done annually as part of clinical management and patients were screened for any incidental findings. All incidental findings were reviewed, recorded in a clinical database and followed up on subsequent visits.
Results: 25 (30%) patients were found to have incidental findings. Liver abnormalities were found in 12 (14.29 %) patients. 11(13.10 %) patients were reported to have coronary artery calcifications. 5 (5.95 %) and 3 (3.57%) patients had thyroid abnormalities and renal cysts, respectively. A malignant lesion was found in 1 patient each in liver and thyroid abnormality subgroup.
Conclusion: Incidental findings are common on thoracic CT scans providing valuable and unexpected findings which warrant investigation by health care providers to exclude malignant processes.
Sonu Sahni1,2*, Sameer Verma1,2, Reeju S Thomas1 , Barbara Capozzi3 and Arunabh Talwar1,2
Hepatitis C Virus infection (HCV) is an increasing public health concern with an estimated 184 million people infected worldwide and approximately 350.000 yearly deaths from HCV-related complications.
Nesrine Gamal and Pietro Andreone*
We report a case of large cell undifferentiated lung carcinoma in a middle aged patient with previously treated tuberculosis and scarring. 20 pack years of smoking history was noted. He presented with metastasis at multiple sites including trochanter, liver and acute bilateral lateral rectus palsy. Chest radiography showed fibrosis of right upper zone with homogenous opacity. Sputum examination for AFB was negative. Computerized tomography of the thorax showed an irregular heterogeneously enhancing mass involving right upper lobe with cavitation, necrosis along with lymph node involvement and the erosion of the 4th rib with liver metastasis. Radiography of hip joint was suggestive of lesser trochanteric metastasis. MRI brain was suggestive of mass at base of brain in parasellar area. Fine needle aspiration cytology and CT guided biopsy confirmed undifferentiated large cell carcinoma of lung. Tuberculosis and smoking may increase the risk of lung scarring and malignancy and pulmonary scarring may be associated with increased lung carcinoma in ipsilateral lung. Clinician needs to be more sensitive to look for malignancy association particularly in patient with or previously treated for tuberculosis and even more emphasis to be laid if scarring of lung is observed.
Sreenivasa Rao Sudulagunta1 *, Shyamala Krishnaswamy Kothandapani2 , Mahesh Babu Sodalagunta3 , Hadi Khorram2 , Mona Sepehrar4 and Zahra Noroozpour1
Systemic Sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs, pronounced alterations in the microvasculature and frequent cellular and humoral immunity abnormalities. The rheumatic involvement of SSc is polymorphic and can reveal the disease or may appear during the course of its progression. Musculoskeletal involvement is dominated by non specific arthralgia, polyarthritis, and bony resorption especially acro-osteolysis. The diagnosis of these rheumatic manifestations is generally based on x rays examination. Musculoskeletal involvement in SSc is generally relieved with Non Steroidal Anti-Inflammatory Drugs (NSAID) or low dose of corticotherapy. The immunosuppressive therapy is used in corticoid-resistant or corticoid-dependent forms such us méthotrexate. The aim of our review is to presents an overview of the different osteoarticular and muscular involvement in SSc, their diagnosis and management.
Nessrine Akasbi*, Fatima Ezzahra Abourazzak and Taoufik Harzy
Sedigheh Mirhashemi1 , Mohammad Hosein Kalantar Motamedi1 *, Amir Hossein Mirhashemi2 and Hamid Reza Rasouli1
We encountered two autopsy cases of huge cardiomegaly with over 1000g in weight. Histochemical characteristics were examined using conventional staining including HE and Azan stains and immunohistochemical staining using antibodies against Complement Component 9 (CC9), RNA Binding Protein Motif 3(RBM3), Endothelial Type NO Synthase (eNOS) and Hypoxic Inducible Factor1α (HIF1). The reactive area with anti CC9 antibody, which presumed to be a marker of hypoxic change of myocardium, overlapped with eosinophilic area by HE and basophilic one by Azan. Although the reactive area with anti CC9 antibody showed relatively weak in the cytoplasm by anti eNOS antibody and no in the nucleus of cardiocytes with anti RBM3 antibody, outside of the reactive area with anti CC9 antibody there were intensive reactivity with anti eNOS antibody in cytoplasm and in a nucleus with anti RBM3 antibody. Anti HIF1 antibody showed weak reactivity with cytoplasm of endocardial cardiocytes and no with cytoplasm of cardiocytes in another area. The results obtained from the present cases revealed that the hypoxic change was equivalent even though the cause of cardiomegaly was deferred between two cases, and conventional staining such as HE and Azan utilized to detect hypoxic change in the heart and immunohistochemical studies seemed to be a useful tool for clarifying the cascade of hypoxic changes in the myocardium.
Satoshi Furukawa1,2*, Mayumi Kataoka1 , Satomu Morita1,2, Akari Uno2 , Masahito Hitosugi2 , Hiroshi Matsumoto1,3 and Katsuji Nishi1,2
A 45-year-old woman with multiple sclerosis was admitted to our hospital after out of hospital cardio-pulmonary resuscitation. The first ECG showed ventricular fibrillation. Following direct current defibrillation and mechanical reanimation, spontaneous circulation was restored and the ECG unremarkable without any signs of ischemia. Coronary angiography showed unobstructed coronary arteries Figure 1, (Panel A). Left ventriculography revealed apical wall obstruction, suggestive of apical aneurysm (Panel B, supplementary videos). Transthoracic echocardiography and Cardiac Magnetic Resonance Imaging (CMR) eventually lead to the diagnosis of a rare case of Apical Hypertrophic Cardiomyopathy (AHC) with ace of spades-form (Panel C,D). The patient underwent Cardioverter-Defibrillator Implantation (ICD) and amiodarone medical therapy for secondary prophylaxis. Patient’s family history and screening for HCM were unsuspicious.
Wiedemann S# *, Heidrich FM# , Speiser U and Strasser RH