Prolonged thrombocytopenia associated with isotretinoin

OBJECTIVE: To report a case of severe prolonged thrombocytopenia possibly associated with isotretinoin. CASE SUMMARY: A 27-year-old white woman developed severe thrombocytopenia and elevated transaminases after 3(1/2) months of treatment with isotretinoin. Prior to the onset of thrombocytopenia, the patient had also received a 10-day course of cephalexin. Rectal bleeding was reported by the patient, who was otherwise asymptomatic. Liver enzyme values returned to normal approximately 1 week after discontinuation of isotretinoin; however, platelet counts required approximately 2 months to normalize. Based on the Naranjo probability scale, possible causality exists between isotretinoin and thrombocytopenia. DISCUSSION: The exact mechanism by which isotretinoin caused thrombocytopenia in this patient is not clearly understood. To our knowledge, only 3 previous cases of isotretinoin-associated thrombocytopenia have been reported. The long recovery process that occurred in our patient is possibly a direct result of the long elimination half-life of both the parent compound and active metabolites of isotretinoin. CONCLUSIONS: Clinicians prescribing isotretinoin should be aware of the potential life-threatening consequence of thrombocytopenia, and a complete blood cell count with platelets should be part of the routine monthly monitoring in all patients receiving isotretinoin therapy.     

Heparin-induced thrombocytopenia

A summary of heparin-induced thrombocytopenia (HIT) is presented. HIT is an adverse drug reaction characterized by thrombocytopenia and a high risk for venous or arterial thrombosis. The frequency of HIT ranges from 1 to 5% of patients receiving heparin with exact frequencies ranging between specific agents. Interestingly, this immune-mediated syndrome is ironically associated with thrombosis, not bleeding, with thrombin formation playing a major role. It is caused by heparin-dependent, platelet-activating antibodies that identifies a self-protein, PF4, bound to heparin that results in an antibody formation. The resulting platelet activation is associated with increased thrombin generation. Typically, the platelet count fall begins 5–10 days after starting heparin, although a rapid platelet count fall can occur in a patient who has antibodies from recent heparin use. Typical causes of HIT as well as the best diagnostic studies and treatment are discussed in this review. HIT was reviewed using a pubmed? search; google scholar? using key words: “Heparin-induced thrombocytopenia”; “heparin”, and “drug AND thrombocytopenia.”     

Heparin-induced thrombocytopenia. A common but controllable condition

Because of the widespread use of heparin in the management of hospitalized patients, heparin-induced thrombocytopenia is a common condition. Clinical diagnosis is based on exclusion. Serious bleeding is uncommon, but thrombosis is a rare complication that can be catastrophic. Prompt recognition of heparin-induced thrombocytopenia and rational use of other antithrombotic agents are essential for optimal patient management.     

Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia is a common immune-mediated drug reaction that can be complicated by life-threatening arterial thrombosis. The diagnosis can be confirmed by demonstrating heparin-dependent release of radiolabeled serotonin from washed normal platelets in the presence of patient serum. However, certain serum samples from these patients produce 14C-serotonin release from some but not other normal donor platelets. We investigated this problem of donor platelet variability by studying the reactivities of 10 serum samples from patients with heparin-induced thrombocytopenia with platelets from 10 normal donors (100 serum and platelet combinations). We observed a marked variability in reactivity for patient serum and platelets from normal donors; this initially appeared random. However, closer examination indicated that the reactivities varied hierarchically. Because heparin-induced thrombocytopenia is caused by binding of heparin-dependent IgG to platelet Fc receptors, we examined whether platelet Fc receptor number or function explained the variability in platelet reactivity. We observed that platelet Fc receptor function, as measured by platelet release associated with heat-aggregated IgG, was highly correlated with platelet reactivity to heparin-induced thrombocytopenia serum samples. No significant correlation, however, was found between Fc receptor number and platelet response. Reaction of murine monoclonal antibodies that activate human platelets by means of the platelet Fc receptors was not predictive of platelet reactivity to heparin-induced thrombocytopenia serum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catastrophic heparin-induced thrombocytopenia/thrombosis syndrome related to the use of a Port-A-Cath in a breast cancer patient receiving chemotherapy

Heparin-induced thrombocytopenia and thrombosis (HIT/T) syndrome is usually triggered by an immune response after repeated administration of heparin. The syndrome is strongly associated with limb deep vein thrombosis and is potentially life-threatening if unrecognized. We describe the case of a patient with compartment syndrome of the left forearm complicated by HIT/T that developed after Port-A-Cath implantation through the left subclavian vein. Prompt recognition of HIT/T, immediate withdrawal of heparin, and timely institution of thrombolytic therapy successfully prevented limb loss.     

Liver cirrhosis and coagulopathy

In patients with chronic liver disease profound coagulation changes and thrombocytopenia may lead to life-threatening bleeding that requires thorough diagnosis and immediate blood product replacement.     

Posttransfusion purpura: the therapeutic value of PlA1-negative platelets

A case of PlA1-associated posttransfusion purpura (PTP) is reported, in which a previously sensitized patient developed life-threatening thrombocytopenia, purpura, hematuria, and bronchial bleeding. The patient was transfused with PlA1-negative single-donor apheresis platelets (from four different donors) on four occasions. The first transfusion resulted in a 1-hour posttransfusion increment of 57 x 10(9) per L. The use of two additional PlA1-negative apheresis platelets provided support for a tracheostomy. Bronchial bleeding leading to respiratory arrest was controlled with a fourth transfusion. All PlA1-negative platelet transfusions resulted in transient increases in the patient's platelet count. This is the first reported case of repeated, transiently effective transfusion of PlA1-negative platelets demonstrated during the acute phase of thrombocytopenia.     

Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management

Summary.  Drug-induced immune thrombocytopenia (DITP) can be triggered by a wide range of medications. Although many cases of DITP are mild, some are characterized by life-threatening bleeding symptoms. The pathogenesis of DITP is complex, in that at least six different mechanisms have been proposed by which drug-induced antibodies can promote platelet destruction. It is possible in many cases to identify antibodies that react with platelets in the presence of the sensitizing drug, but the required testing is technically demanding and not widely available. Therefore, a decision on whether to discontinue an implicated medication in a patient suspected of having DITP must be made on clinical grounds. An algorithm is available that can be helpful in assessing the likelihood that a particular drug caused thrombocytopenia, but the most important aspects of patient management are a high index of suspicion and a careful history of drug exposure in an individual who presents with acute, often severe thrombocytopenia of unknown etiology. How drugs induce platelet-reactive antibodies and how, once formed, the antibodies cause platelet destruction following exposure to the drug is poorly understood. Further studies to address these issues and characterize more completely the range of drugs and drug metabolites that can cause DITP are needed.     

Thrombocytopenia

Thrombocytopenia is defined as a platelet count of less than 150 × 103 per μL. It is often discovered incidentally when obtaining a complete blood count during an office visit. The etiology usually is not obvious, and additional investigation is required. Patients with platelet counts greater than 50 × 103 per μL rarely have symptoms. A platelet count from 30 to 50 × 103 per μL rarely manifests as purpura. A count from 10 to 30 × 103 per μL may cause bleeding with minimal trauma. A platelet count less than 5 × 103 per μL may cause spontaneous bleeding and constitutes a hematologic emergency. Patients who present with thrombocytopenia as part of a multisystem disorder usually are ill and require urgent evaluation and treatment. These patients most likely have an acute infection, heparin-induced thrombocytopenia, liver disease, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation, or a hematologic disorder. During pregnancy, preeclampsia and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are associated with thrombocytopenia. Patients with isolated thrombocytopenia commonly have drug-induced thrombocytopenia, immune thrombocytopenic purpura, pseudothrombocytopenia, or if pregnant, gestational thrombocytopenia. A history, physical examination, and laboratory studies can differentiate patients who require immediate intervention from those who can be treated in the outpatient setting. Treatment is based on the etiology and, in some cases, treating the secondary cause results in normalization of platelet counts. Consultation with a hematologist should be considered if patients require hospitalization, if there is evidence of systemic disease, or if thrombocytopenia worsens despite initial treatment.     

抗凝与出血:临床决策的平衡与选择

抗凝药物治疗和预防血栓性疾病的有效性早已得到证实,但抗凝治疗在显著降低血栓事件发生风险的同时,可能导致出血并发症,严重者可致命。临床实践中存在医师和患者过分顾虑抗凝治疗出血风险的现象,抗凝药物的使用率远低于预期,故评估抗凝治疗的获益与风险,制定合理的抗凝治疗方案,具有重要意义。临床需结合患者具体情况选择适用的评估量表,综合评估抗凝治疗,确定合适抗凝药物及剂量,加强抗凝治疗管理,在抗凝与出血之间找到平衡,作出合理选择。     

Acute multi-vessel coronary stent thrombosis

Background: Coronary artery stent thrombosis is a rare but often fatal complication associated with percutaneous coronary intervention (PCI) using both bare-metal stents and drug-eluting stents. Although strict adherence to dual anti-platelet therapy (aspirin plus clopidogrel) minimizes this risk, stent thrombosis will still occur in rare patients, leading to acute, subacute, or late life-threatening acute coronary syndromes. Objectives: To present a rare case of acute stent thrombosis involving multiple vessels to increase awareness of this life-threatening condition among emergency physicians, and to review the current guidelines for anti-platelet therapy in this patient population. Case Report: A 52-year-old man who underwent PCI using drug-eluting stents in two separate coronary vessels presented to the Emergency Department within 2 h of discharge from the hospital with chest pain, dynamic electrocardiogram changes, and elevated cardiac markers. Despite compliance with the current recommendations for post-PCI anti-platelet therapy, urgent repeat catheterization revealed total thrombotic occlusion of both stents, requiring urgent repeat intervention. Conclusion: Despite patient compliance with the currently recommended anti-platelet regimen after stent therapy for coronary artery disease, acute stent thrombosis remains a rare but life-threatening risk in both the immediate and delayed post-intervention period. In addition, premature cessation of this anti-platelet therapy stands as the greatest risk factor for such thrombotic events. This case is presented to inform emergency physicians of the current post-PCI anticoagulation recommendations to help mitigate the risk of such complications.     

Argatroban for suspected heparin-induced thrombocytopenia: contemporary experience at a large teaching hospital

Heparin-induced thrombocytopenia requires immediate alternative anticoagulation to prevent or treat thromboembolic complications. Argatroban was approved based on multiple-center studies from the 1990s, but subsequent changes in prevailing awareness, diagnostic testing and therapeutic strategies for heparin-induced thrombocytopenia might affect results of argatroban therapy. Charts were retrospectively reviewed from patients administered argatroban for suspected heparin-induced thrombocytopenia over 22 months at a single large university hospital. Twenty-seven patients, most in intensive care units, received a median 0.5 microg/kg/min argatroban over a median 5.5 days. Patients had isolated heparin-induced thrombocytopenia (n = 10), had heparin-induced thrombocytopenia with thrombosis (n = 9), or lacked active heparin-induced thrombocytopenia (n = 8) on final analysis. New thromboses (14.8%), progression of preexisting thromboses (0%), amputation secondary to heparin-induced thrombocytopenia (0%), death (22.2%), bleeding requiring transfusion (3.7%), and any bleeding (22.2%) compared favorably with older multiple-center reports. Deaths occurred mainly with preexisting multiple-organ failure. In contemporary "real world" use, argatroban provides safe and effective anticoagulation, strengthening the mandate to initiate alternative anticoagulation whenever heparin-induced thrombocytopenia appears likely.     

EDTA依赖性假性血小板减少1例

血小板减少为临床常见症状,表现为由于各种原因导致的血小板计数结果低于参考值下限。当血小板减少时可出现一系列症状,如皮肤淤血、鼻出血、口腔黏膜出血等,严重者可出现内脏出血、脑出血甚至危及生命。乙二胺四乙酸二钾(EDTA-K2)为血液分析的常用抗凝剂,但有时会引起血小板聚集,使血小板计数假性减少,临床诊断为EDTA依赖性假性血小板减少症(EDTA-PTCP)。赤壁市蒲纺医院(同济赤壁医院)于2019年12月16日收治1例血小板减少的患者,前后两次血常规检测所得血小板计数结果出现较大偏差,使用EDTA-K2抗凝管检测血常规时,患者的血小板数值低于正常参考值下限(26×10^9/L);改用肝素抗凝管检测时,患者的血小板数值在正常值参考范围内。经血小板人工计数及血涂片复片染色检查等手段复检后,均显示患者血小板数值在正常值参考范围内,证实了该例患者为EDTA-PTCP。     

Hemostasis in Liver Disease: Implications of New Concepts for Perioperative Management

The hemostatic profile of patients with liver diseases is frequently profoundly different from that of healthy individuals. These complex alterations lead to abnormal results from routine laboratory tests, but because of the nature of these assays, they fail to accurately represent the patient’s hemostatic state. Nevertheless, based on abnormal laboratory coagulation values, it has long been assumed that patients with liver disease have a natural bleeding tendency and are protected from thrombosis. This assumption is false; the average patient with liver disease is actually in a state of “rebalanced hemostasis” that can relatively easily be tipped toward both bleeding and thrombosis. The new paradigm of rebalanced hemostasis has strong implications for the clinic, which are presented in this review. There is no evidence that prophylactic transfusion of plasma helps to prevent procedure-related bleeding. In addition, the presence of independent risk factors such as poor kidney status or infections should be carefully assessed before invasive procedures. Furthermore, central venous pressure plays an important role in the risk of bleeding in patients with liver diseases, so during procedures, a restrictive infusion policy should be applied. Finally, thrombosis prophylaxis should not be withheld from patients with cirrhosis or acute liver failure, and clinicians should be alert to the possibility of thrombosis occurring in these patients.     

Use of Point-of-Care Ultrasound to Facilitate Guidance and Intrauterine Placement of a Foley Urinary Catheter to Tamponade Life-Threatening Postprocedure Hemorrhage Caused by Disseminated Intravascular Coagulation

BackgroundSevere vaginal hemorrhage caused by disseminated intravascular coagulation (DIC) after dilation and evacuation is a rare but life-threatening situation that can be difficult to manage. Obtaining hemostasis in such a patient with heavy vaginal bleeding secondary to DIC can be difficult. One technique involves the use of a urinary bladder catheter inserted into the uterus that is inflated to apply pressure on the endometrium, allowing for tamponade of the bleeding.Case ReportA 36-year-old female gravida 2 para 0 at 21 weeks’ gestation presented to the emergency department after being transferred from another facility for a higher level of care available at our facility, after a dilation and evacuation procedure that was indicated because of intrauterine fetal demise. The physical examination was significant for an ill-appearing female with active heavy vaginal bleeding. Resuscitation was initiated with packed red blood cells, cryoprecipitate, and platelets. Because of her thrombocytopenia, the development of DIC was suspected. Point-of-care ultrasound (POCUS) was performed and showed a thickened endometrial stripe with evidence of multiple anechoic foci, which were thought to represent intrauterine clots. To tamponade the bleeding, a 30-cc standard Foley urinary bladder catheter was placed into the uterus, using POCUS for guidance, to attempt to induce hemostasis via tamponade of the bleeding after inflation of the catheter balloon. Placement of an intrauterine urinary catheter to enable tamponade can be useful for the management of uncontrolled hemorrhage, but can be difficult to accomplish without use of POCUS for guidance. POCUS enabled us to accomplish accurate intrauterine placement of the urinary catheter and confirmation of a properly placed catheter balloon within the uterus.Why Should an Emergency Physician be Aware of This?Menorrhagia in the emergency department can be difficult to manage, especially in the setting of DIC. Placement of an intrauterine urinary catheter can be useful in management but may be difficult for the inexperienced provider. POCUS can be used to guide the catheter into place and confirm the location once the balloon is inflated.     

Bleeding complications associated with peritoneal dialysis catheter insertion.

OBJECTIVE: To identify the incidence of bleeding complications associated with peritoneal dialysis catheter insertion. DESIGN: Retrospective review at a tertiary-care center of all double-cuffed Tenckhoff catheters placed surgically from 1 January 1992 to 1 October 2003 to identify the incidence of major bleeding complications occurring with catheter insertion. Major bleeding episodes were defined as > or = 3% decline in hematocrit, or the need for surgical intervention or blood transfusion within 2 weeks of insertion. RESULTS: 292 catheters had been inserted in 263 patients. Six patients satisfied the criteria for a major bleeding event, for a major bleeding complication rate of 2%. Bleeding was associated with perioperative anticoagulation in 3 patients, uremia and thrombocytopenia in 1 patient, aspirin use and thrombocytopenia in 1 patient, and 1 patient experienced intraoperative bleeding. Coagulation parameters were not obtained prior to the procedure in 2 of the 6 patients. CONCLUSION: The rate of serious bleeding complications related to catheter insertion is low and usually associated with anticoagulation. Holding anticoagulation therapy for a minimum of 24 hours during the postoperative period should eliminate much of the risk. Coagulation parameters should also be obtained and corrected preoperatively.     

Uterine Artery Pseudoaneurysm: A Life-Threatening Cause of Vaginal Bleeding in the Emergency Department

Background

Vaginal bleeding is a common presenting complaint in the emergency department (ED); life-threatening hemorrhage is rare. Uterine artery pseudoaneurysm (UAP) is an uncommon but potentially life-threatening cause of vaginal bleeding that is most likely to present primarily to EDs, given its delayed postpartum or postoperative presentation.

Effect of the somatostatin analogue octreotide acetate on hemostasis in humans.

Octreotide acetate is a somatostatin analogue that has been shown to ameliorate the side effects of excessive secretion of hormone from benign and malignant tumors. The ability of this drug to inhibit the growth of malignant cells and to control gastrointestinal hemorrhage will prompt additional clinical trials. Because some of these patients may have thrombocytopenia, platelet dysfunction, or a coagulopathy, we studied tests of platelet function and blood coagulation in 15 patients before and after 14 days of therapy with octreotide acetate at a dosage of 500 micrograms three times daily. We found no substantial change in the results of these tests, and no patient experienced bleeding or thrombosis. These results suggest that octreotide acetate does not adversely affect platelet function or the coagulation system in humans.     

Recombinant FVIIa in the management of intracerebral haemorrhage in severe thrombocytopenia unresponsive to platelet-enhancing treatment

Intracranial haemorrhage (ICH) is a dramatic and potentially life-threatening presentation of children with thrombocytopenia. Management is limited to supportive care. Recent evidence suggests that ongoing bleeding following the initial ICH may result in greater neurological morbidity and mortality. Haemostatic agents, including recombinant factor VIIa (rFVIIa), a product licensed for use in patients with haemophilia and inhibitors, may be helpful in reducing bleeding in children with refractory thrombocytopenia. We present the case of a 16-year-old girl with severe refractory immune thrombocytopenia, who presented with a major ICH and responded to treatment that included rFVIIa and platelet transfusions. The dose of rFVIIa was empirically chosen and based on reported cases in the literature. The case highlights a number of issues regarding off-label use of rFVIIa and demonstrates the need to prospectively collect accurate information on the off-label use of this new potentially useful medication.     

Severe thrombocytopenia possibly associated with TMP/SMX therapy

OBJECTIVE: To report a case of possible severe, life-threatening thrombocytopenia associated with trimethoprim/sulfamethoxazole (TMP/SMX) therapy. CASE SUMMARY: A 54-year-old white woman received a 10-day course of TMP/SMX for treatment of chronic sinusitis. One day after finishing the course of TMP/SMX therapy, the presented to the emergency department because of the development of scattered petechiae on both hands and blood blisters in her mouth. On admission, her complete blood cell count results revealed a severely low platelet count of 2 x 10(3)/mm3. Other laboratory test results were normal, except for elevated blood glucose (nonfasting blood glucose). TMP/SMX was believed to be the most likely cause of thrombocytopenia. She was treated successfully with a transfusion of 2 units of platelets and oral prednisone. Her platelet count increased to 110 x 10(3)/mm3 4 days after discontinuation of TMP/SMX. She was discharged on hospital day 5. On follow-up (2 wk after hospital discharge), her platelet count was normal (351 x 10(3)/mm3). DISCUSSION: TMP/SMX has been implicated as a cause of thrombocytopenia, which is defined as platelet count < 150 x 10(3)/mm3. Although it is uncommon, spontaneous severe bleeding may occur when platelet count decreases to < or = 10 x 10(3)/mm3. Thrombocytopenia associated with TMP/SMX appears to be an immune-mediated process resulting in platelet destruction by drug-dependent platelet antibodies. Treatment of thrombocytopenia associated with TMP/SMX therapy includes discontinuation of the offending drug and the use of corticosteroids. Platelet transfusion and intravenous immunoglobulin may be required in some patients. CONCLUSIONS: Thrombocytopenia associated with TMP/SMX therapy can be serious or life threatening because it may result in significant bleeding complications. This hematologic adverse effect of TMP/SMX may occur even with the usual recommended dosage and duration of therapy. Careful monitoring of complete blood cell count, including platelet count, before and during TMP/SMX therapy is suggested.