Acquired Coagulation Disorders Research Articles

Emicizumab: the hemophilia A game-changer.

In hemophilia, the unmet needs regarding adherence to prophylaxis and lack of effective long-term prophylaxis regimens, especially in patients with inhibitors, led to the production of emicizumab, the first non-factor medicine for subcutaneous administration in patients with severe and moderate hemophilia A with or without factor VIII inhibitors. This review describes the research steps behind the development of this game-changing medication as well as its success in the prophylaxis of bleeding episodes, as witnessed by the results of pivotal clinical trials but also by real-life use in the frame of a still expanding global market. We also discuss potential and actual adverse events and the nuances related to clinical use, such as laboratory monitoring, development of neutralizing antidrug antibodies, risk of thrombosis/hypercoagulability and role in the management of surgical operations. The potential of emicizumab to prevent bleeding in other congenital and acquired coagulation disorders is also outlined.

Bleeding-Coagulation System Disorders and Retina (Disseminated Intravascular Coagulopathy, Von Willebrand Disease, Vitamin K Deficiency, Hemophilia A and Hemophilia B)

Coagulation system disorders result from the imbalance between procoagulant and anticoagulant activity and are classified as congenital and acquired coagulation disorders. There are dozens of diseases under these headings, and these diseases can cause serious complications in the anterior and posterior segment structures of the eye and orbit. Among these complications, there may be situations such as subconjunctival hemorrhage, which can be resolved by spontaneous resorption, or it can be seen in cases such as retinal-choroidal hemorrhage and ischemia that may result in severe vision loss. In ophthalmology practice, evaluating and treating ocular complications of a patient with a suspected bleeding disorder is very important in terms of visual prognosis. Especially in the treatment of vitreoretinal hemorrhages, vitreoretinal surgery is seen as an important and effective treatment protocol. To prevent possible complications that may occur during surgery, precautions should be taken to reduce the risk of hemorrhage with a multidisciplinary approach. This review will discuss the approach to orbital complications and retinal pathologies in coagulation system disorders.

Behandlungsoptionen bei Meno-Metrorrhagie

Heavy and irregular menstrual bleeding (menorrhagia/metrorrhagia; MM) is common and affects between 10 and 30% of women of reproductive age. MM is associated with numerous clinical symptoms and a significant reduction in quality of life. The most important etiological factors of MM include endometrial polyps, myomas, adenomyosis, hyperplasia/malignancy, hereditary or acquired coagulation disorders, ovulatory dysfunction, and iatrogenic causes. The only definitive and therefore most effective treatment of MM is hysterectomy. Alternatives are uterus-conserving ablative approaches, e.g. endometrial resection (RS) and endometrial ablation (EA). In the case of hysterectomy, laparoscopic supracervical hysterectomy (LASH) is the method of first choice, if there are no specific reasons to remove the cervix. Conservative, non-surgical therapies of MM are available, including levonorgestrel-releasing intrauterine devices, oral/parenteral progestogens, oral/parenteral combination contraceptives, tranexamic acid, non-steroidal antirheumatics, selective progesterone receptor modulators, and gonadotropin releasing hormone agonists/antagonists.

Thrombophilia and Pregnancy

Abstract Leading cause of death in pregnant women still remains venous thromboembolism, with an incidence of 1.4 to 4.9 per 100,000 pregnancies. A special group of inherited and acquired coagulation disorders associated with a susceptibility to thrombosis is thrombophilia. Physiological changes during the pregnancy also contribute to the occurrence thromboembolic diseases (VTE) in pregnancy. Total rate of venous thromboembolism is 100 per 100,000 pregnancies and 200 per 100,000 births. Etiopathogenesis of obstetric complications in thrombophilia is not clearly defined, which is one of the reasons for the occasional failure of therapy. In pregnancies with hereditary thrombophilia the oxidative stress is considered to be a cause of complications, similar to preeclampsia. Based on the findings so far, additional research should clarify questions regarding the anticoagulants role in pregnancy loss prevention. In this paper, we analyze the effect of the screening on pregnancy outcomes, consider the justification for the use of anticoagulation therapy in difficult situations, discuss about previous knowledge in the field and argue the use of new specific protocols. In short, we address the justification for prescribing anticoagulants and evaluation of their effect within thrombophilia therapeutic strategies.

Spontaneous Spinal Subdural Hematoma Secondary to Hemophilia A and Zanubrutinib

Spontaneous spinal subdural hematomas (SSH) are rare occurrences that can occur most commonly secondary to vascular malformations or coagulopathies. Only a small fraction of spontaneous SSHs are caused by acquired coagulation disorders such as leukemia, hemophilia, and thrombocytopenia. This case report describes a patient with a history of Guillain–Barré syndrome (GBS), hemophilia A, and mantle cell lymphoma, on zanubrutinib therapy, a Bruton tyrosine kinase inhibitor associated with a risk of spontaneous hemorrhage. This patient developed a spontaneous spinal subdural hematoma, most likely due to the zanubrutinib therapy and exacerbated due to hemophilia. Treatment was delayed due to the patient's history of GBS that confounded the clinical diagnosis. This case is the first report of a spontaneous SSH in a patient on zanubrutinib, highlighting the need for a high index of suspicion for CNS hemorrhage in patients on Bruton's tyrosine kinase (BTK) inhibitor therapy.

Towards personalized antithrombotic management with drugs and devices across the cardiovascular spectrum.

Intravascular thrombus formation and embolization are among the most frequent events leading to a number of cardiovascular conditions with high morbidity and mortality. The underlying causes are stasis of the circulating blood, genetic and acquired coagulation disorders, and reduced antithrombotic or prothrombotic properties of the vascular wall (Virchow's triad). In the venous system, intravascular thrombi can cause venous thrombosis and pulmonary and even peripheral embolism including ischaemic stroke [through a patent foramen ovale (PFO)]. Thrombi in the left atrium and its appendage or ventricle form in the context of atrial fibrillation and infarction, respectively. Furthermore, thrombi can form on native or prosthetic aortic valves, within the aorta (in particular at sites of ulcers, aortic dissection, and abdominal aneurysms), and in cerebral and peripheral arteries causing stroke and critical limb ischaemia, respectively. Finally, thrombotic occlusion may occur in arteries supplying vital organs such the heart, brain, kidney, and extremities. Thrombus formation and embolization can be managed with anticoagulants and devices depending on where they form and embolize and on patient characteristics. Vitamin K antagonists are preferred in patients with mechanical valves, while novel oral anticoagulants are first choice in most other cardiovascular conditions, in particular venous thromboembolism and atrial fibrillation. As anticoagulants are associated with a risk of bleeding, devices such as occluders of a PFO or the left atrial appendage are preferred in patients with an increased bleeding risk. Platelet inhibitors such as aspirin and/or P2Y12 antagonists are preferred in the secondary prevention of coronary artery disease, stroke, and peripheral artery disease either alone or in combination depending on the clinical condition. A differential and personalized use of anticoagulants, platelet inhibitors, and devices is recommended and reviewed in this article.

Hypercoagulopathy, acquired coagulation disorders and anticoagulation before, during and after extracorporeal membrane oxygenation in COVID-19: a case series.

Thromboembolism and bleeding contribute to Coronavirus disease 2019 (COVID-19)'s morbidity and mortality and are also frequent complications of venovenous extracorporeal membrane oxygenation (vvECMO). As the interaction of the underlying pathologies caused by vvECMO in COVID-19 is barely understood, we designed this study to better differentiate coagulation disorders in COVID-19 patients before, during and after vvECMO-support. Observational case series, six consecutive patients with Coronavirus acute respiratory distress syndrome supported with vvECMO treated in the anaesthesiologic ICU in a third level University ECMO-centre. We measured routine coagulation parameters and assessed coagulation factors. We also conducted advanced von Willebrand factor (VWF) multimer analysis, platelet aggregometry and immunological screening. We identified various phases of coagulation disorders: Initially, intensely activated coagulation with highly increased VWF and factor VIII activity in acute COVID-19, then severe acquired von Willebrand syndrome and platelet dysfunction during vvECMO leading to spontaneous bleeding and finally, hypercoagulopathy after vvECMO explantation. Five of six patients developed immunological abnormalities enhancing coagulation. Coronavirus-induced coagulopathy and bleeding disorders during vvECMO cannot be discriminated via 'routine' coagulation tests. Precise and specific analyses followed by the appropriate treatment of coagulation disorders may help us develop tailored therapeutic concepts to better manage the phases described above.

An Extremely Rare Association of Alcohol-Induced, Necrotizing, Acute Pancreatitis and Giant Dissecting Hematoma of the Gastric Wall with Hemorrhagic Shock: a Case Report

Intramural gastric-wall hemorrhage is an extremely rare condition associated with acute pancreatitis. To the authors’ knowledge, at present, only four cases have been reported in the international literature, the case reported herein being the fifth. We performed an extensive literature review on the issue and compared our data with those of similar reports. A 69-year-old man was admitted to the emergency department complaining of severe epigastric pain with tenderness and muscle guarding. After initial diagnostic workup, acute pancreatitis associated with intramural gastric mass was diagnosed. Upfront conservative treatment was begun, but the patient worsened, with class 3 hemorrhagic shock appearing. The patient underwent emergent explorative laparotomy that revealed a huge intraparietal gastric hematoma requiring total gastrectomy to control bleeding. Because an intramural gastric-wall hematoma is a very rare condition and usually associated with both primary and acquired coagulation disorders, it requires a high suspicion index for a prompt diagnosis. Small gastric-wall hematomas can be treated conservatively, especially when associated with anticoagulation therapy, but surgery must always be considered for patients who fail conservative or angiographic treatment. Furthermore, surgery may be considered an upfront therapy for emergent cases. Surgery remains the procedure of choice in all cases not responding to conservative therapy and when hemorrhagic shock develops.

Alteraciones adquiridas de la coagulación

Acquired coagulation disorders: Acquired coagulation disorders tend to be diagnosed in adulthood in patients without a history of coagulopathy. A large part of them are secondary to other underlying pathologies. The physiopathology of acquired coagulopathies differs greatly from one to another. Disseminated intravascular coagulation (DIC) is secondary to an activation of coagulation with secondary consumption of factors. Chronic liver disease leads to hypoproduction of coagulation factors and regulatory proteins of hemostasis. Acquired hemophilia A is secondary to production of a factor VIII inhibitor antibody. Lastly, both acquired von Willebrand disease and acquired factor XIII deficiency have several possible causes. Hemorrhagic symptoms vary from one to another, ranging from an absence of or very mild symptoms in certain cases of DIC or liver disease to life-threatening bleeding in acquired hemophilia A. Likewise, in the laboratory, each pathology has certain alterations by which a definitive diagnosis is confirmed. In general, treatment of the underlying causes is essential for controlling these coagulopathies and control of hemorrhagic symptoms is of vital importance.

Current trends in blood coagulation studies

Blood coagulation occurs in flow or stasis conditions, it involves components of cell hemostasis and enzymatic cascades of reactions; it serves to stop bleeding yet it can lead to life-threatening blood thrombi. Despite the fact that a complete list of coagulation proteins was well known for decades, in recent years numerous facts has accumulated about its structure and regulation. All that has led to the creation of new methods for diagnosing of blood coagulation disorders and methods for their correction. Congenital and acquired coagulation disorders are still an acute clinical problem. This review shows modern ideas about the structure and functioning of the blood coagulation system in various conditions.

КЛІНІЧНИЙ ВИПАДОК ТРОМБОЕМБОЛІЇ У КОНЯ

За результатом проведеного патологоанатомічного дослідження встановлено, що ускладненням хронічного тромбозу великих артеріальних судин тазових кінцівок коня став тромбоз черевної аорти і, як наслідок, зміщення тромбу з аорти в отвір краніальної брижової артерії з її повною облітерацією. Вище зазначене призвело до тромбоемболії каудальної частини товстого відділу кишечнику і, як наслідок, – розвитку кольок, порушення живлення та іннервації стінки кишечнику, що, в свою чергу, призвело до інвагінації кишечнику з подальшим розривом гілок брижової артерії, черевною кровотечею. Черевна порожнина містила велику кількість пухких згустків крові світло червоного кольору. В товщі брижі і під очеревиною – дифузно розсіяні великі кров’янисті інфільтрати. Брижа малої ободової кишки частково розірвана, краї просочені кровʼю. Середня частина ободової кишки була інвагінована в просвіт ампулоподібного розширення прямої кишки, просвіт останнього з ознаками вираженої дилятації. У просвіт прямої кишки, через отвір діаметром 18 см. в стінці, частково були зміщенні петлі тонкого відділу кишечнику

Acquired coagulation disorders

Acquired coagulation inhibitors have become a popular area of research because they cause severe bleeding tendency in many patients. The use of acquired coagulation inhibitors requires rapid and precise diagnosis. Some acquired coagulation inhibitors show prolongation in the activated partial thromboplastin time (APTT) and/or prothrombin time (PT). To diagnose these disorders, mixing test is very useful. However, lupus anticoagulant related disorders, such as lupus anticoagulant hypoprothrombinemia syndrome (LAHPS), are difficult to diagnose because they are sometimes associated with a reduction in factor VIII and are thus difficult to distinguish from acquired hemophilia. Acquired factor XIII deficiency and acquired von Willebrand syndrome (AvWS) are easily overlooked because they show normal value in several patients with APTT and PT. Here I describe the diagnostic method for these disorders. In particular, five acquired coagulation inhibitors that appear to be clinically significant are studied.

Circulating Plasminogen Activator Inhibitor-1 (PAI-1) Is Reduced By In Vivo Thrombin Generation and Subsequent Formation of Activated Protein C (APC)

Background: APC has been suggested to contribute to a hyperfibrinolytic state in various acquired coagulation disorders, including coagulopathies induced by trauma and sepsis. However, in vivo evidence for the proposed underlying mechanism of proteolytic degradation of PAI-1 by APC remains inconclusive. Recently, we have shown increased APC generation in response to in vivo thrombin formation in carriers of the factor V Leiden mutation (FVL). In this approach of stimulated hemostasis activity pattern evaluation (SHAPE), in vivo thrombin formation was triggered by low-dose administration of recombinant activated factor VII (rFVIIa). Aim of the present study was to investigate the resulting effects on the fibrinolytic system. Methods: The study population consisted of 30 FVL carriers (thereof 13 with a history of venous thromboembolism) and 15 healthy controls. Blood samples were collected immediately before and during a period of 8 hours following injection of 15 µg/kg rFVIIa. Plasma levels of APC were quantified using an oligonucleotide-based enzyme capture assay (OECA). Other monitored parameters included plasma levels of prothrombin activation fragment 1+2 (F1+2), tissue-type plasminogen (t-PA), PAI-1, plasminogen, α2-antiplasmin, plasmin-α2-antiplasmin complexes (PAP), soluble fibrin monomers, d-dimer, and thrombin-activatable fibrinolysis inhibitor (TAFI). Results: At baseline, FVL carriers showed higher median levels of APC in comparison to the controls (1.39 vs. 0.86 pmol/L, P=.001), higher PAI-1 levels (30.1 vs. 15.3 ng/mL, P=.002) and lower plasminogen levels (94.8 vs. 110.4%, P=6·10-4). The other baseline parameters did not differ significantly. In both cohorts a comparable increase of F1+2 was observed after administration of rFVIIa, whereas APC increased more (P=.004) in FVL carriers (by 6.40 pmol/L) than in healthy controls (by 2.14 pmol/L), Concurrently, median PAI-1 levels decreased more (P=.007) in FVL carriers (by 19.8 pmol/L) than in healthy controls (by 8.0 pmol/L) (Figure 1). TAFI levels decreased temporarily, from 104.8 to 94.4% (P=.007) in FVL carriers and from 105.0 to 92.1% (P=2·10-4) in healthy controls. PAP levels increased from 164 to 209 ng/mL (P<10-4) in FVL carriers and from 154 to 189 ng/mL (P=.023) in the control group. The extent of these changes did not differ between the two cohorts. D-dimer level increased only in FVL carriers, from 0.34 to 0.41 mg/L (P=.008). t-PA and the other parameters did not show significant changes after rFVIIa administration. Conclusion: Increased APC formation rates in FVL carriers were associated with a greater decline of PAI-1 levels in the absence of interfering changes in t-PA levels. These data provide further in vivo evidence that APC down-regulates PAI-1. Overall, the SHAPE approach utilized here does not induce a significant profibrinolytic response, even in patients with thrombophilia. Disclosures Reda: Grifols: Honoraria; Shire: Honoraria. Winterhagen:SOBI: Honoraria. Berens:Pfizer: Honoraria; Shire: Honoraria; Biotest: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Baxter: Honoraria. Müller:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Siemens: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Oldenburg:CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding, Speakers Bureau; Swedish Orphan Biovitrum: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Takeda (Shire): Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau. Rühl:CSL Behring: Honoraria; Bayer: Honoraria; Shire: Honoraria; SOBI: Honoraria; Sanofi Genzyme: Honoraria; Grifols: Honoraria.

The relationship between coagulation disorders and the risk of bleeding in cirrhotic patients

Introduction and ObjectivesFor long, bleeding in cirrhotic patients has been associated with acquired coagulation disorders. The aim of our study was to investigate the impact of acquired coagulation disorders on bleeding risk in cirrhotic patients. Materials and methodsBlood samples were collected from 51 cirrhotic patients with (H+) or without (H−) bleeding events and 50 controls matched by age and sex. Thrombin generation was assessed as endogenous thrombin potential (ETP). Hemostatic balance was assessed by means of ratios of pro- to anticoagulant factors and by ETP ratio with/without protein C (PC) activator (ETP ratio). ResultsBleeding events occurred in 9 patients (17.6%). Compared with controls, VIII/anticoagulant factors, VII/PC and XII/PC were significantly higher in (H+) patients. No significant difference as regards all ratios across patient groups was detected. ETP ratio was significantly higher in (H+) patients than in controls (p=0.017). However, there was no significant difference between patient groups as regards ETP ratio. ConclusionHemostatic balance is shifted toward a hypercoagulability state even in cirrhotic patients who experienced bleeding. These findings provide evidence against traditional concept of hemostasis-related bleeding tendency in cirrhotic patients.

Comprehensive coagulation assays toward reflecting clinical phenotype for acquired coagulation disorders.

Comprehensive coagulation assays toward reflecting clinical phenotype for acquired coagulation disorders.

Reference intervals of citrated-native whole blood thromboelastography in premature neonates

Abstract Background Bleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated. Aims To evaluate TEG in preterm neonates, and to assess their reference ranges. Methods One hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates. Results Comparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values. Conclusions These results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning.

Reference intervals of citrated-native whole blood thromboelastography in premature neonates

BackgroundBleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated. AimsTo evaluate TEG in preterm neonates, and to assess their reference ranges. MethodsOne hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates. ResultsComparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values. ConclusionsThese results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning.

Nontumoral portal vein thrombosis in patients awaiting liver transplantation.

Portal vein thrombosis (PVT) occurs in approximately 2%-26% of the patients awaiting liver transplantation (LT) and is no longer an absolute contraindication for LT. Nearly half of PVT cases are accidentally found during the LT procedure. The most important risk factor for PVT development in cirrhosis may be the severity of liver disease and reduced portal blood flow. Whether other inherited or acquired coagulation disorders also play a role is not yet clear. The development of PVT may have no effect on the liver disease progression, especially when it is nonocclusive. PVT may not increase the risk of wait-list mortality, but it is a risk factor for poor early post-LT mortality. Anticoagulation and transjugular intrahepatic portosystemic shunt (TIPS) are 2 major treatment strategies for patients with PVT on the waiting list. The complete recanalization rate after anticoagulation is approximately 40%. The role of TIPS to maintain PV patency for LT as the primary indication has been reported, but the safety and efficacy should be further evaluated. PVT extension and degree may determine the surgical technique to be used during LT. If a "conventional" end-to-end portal anastomotic technique is used, there is not a major impact on post-LT survival. Post-LT PVT can significantly reduce both graft and patient survival after LT and can preclude future options for re-LT.

Coagulation disorders

For clinicians, who are not experienced in hemostasis and thrombosis, coagulation and coagulation disorders remain a ‘book of seven seals’ (1). This may be due, at least in part, to the complexity of the hemostatic apparatus and its interaction with inflammatory processes and immune mechanisms, all of which require detailed theoretical knowledge, practical experience, and continuous medical education (CME). More recently, the use of direct oral anticoagulants, which have specific pharmacological targets and pharmacodynamics distinct from those of vitamin K antagonists, heparins, or the pentasaccharide fondaparinux, has created insecurities and concerns among clinicians. Some of these concerns result from the fact that these novel agents with their superior safety profile impact on standard coagulation screening tests (such as prothrombin time and activated partial thromboplastin time) in a way that is different from conventional anticoagulants. This theme issue of Hamostaseologie should facilitate the readers’ access to several acquired coagulation disorders and assist to overcome fundamental problems of understanding hemostasis or, metaphorically spoken, to ‘break some of the seals’ of hemostasis and thrombosis textbooks. As third part in a series of reviews, the current edition also reflects several highlights of the GTH Congress 2015 (2, 3, 4). In his article, Medcalf provides an upto-date view on fibrinolysis, demonstrating that tissue-type plasminogen activator (t-PA)-mediated conversion of plasminogen into plasmin is not solely designed to remove fibrin deposits and blood clots in a self-regulated proteolytic process (5). Importantly, it is shown that t-PA and plasmin have pleotrophic effects and other substrates than fibrin such as prion proteins, amyloid-β, and misfolded or aggregated proteins. Thus, t-PA can act in a nonfibrinolytic (i.e., plasmin-independent) manner and have multiple effects on cerebral functions (e.g., synaptic plasticity, neurotransmission, visual processing, learning and memory). The author therefore concludes that the “original concept for the fibrinolytic system, being focused on fibrin, is a massive understatement” (5). Tiede et al. report on recent advances in the management of acquired hemophilia A (AHA) (6). At an incidence of about 1.3 cases per million people (7), AHA is a rare but challenging bleeding disorder caused by inhibitory autoantibodies against coagulation factor (F) VIII. Apart from hemostatic management to control active bleeding, immunosuppressive treatment is mandatory in AHA to achieve remission. However, the outcome of AHA remains highly variable. Therefore, clinically valid prognostic factors for remission are urgently required. Recently, the GTH-AH (01/2010) study, a multicenter trial conducted under the leadership of Andreas Tiede, has demonstrated for the first time that residual FVIII activity and inhibitor

Abklärung einer erworbenen Blutungsneigung

Patients with acquired bleeding disorders are often a diagnostic challenge in internal medicine. Which diagnostic work up is necessary in these patients and which coagulation tests are useful? Analysis and diagnostic workup in the daily practice are discussed according to review publications in this field and existing clinical evidence. First important step is the bleeding history of the patient. The different signs of bleeding are important hints for the cause. The global assays Quick (PT) and PTT in combination with platelet count and function reveal a primary knowledge of the kind of the acquired bleeding disorder. In addition special coagulation tests normally lead to the exact diagnosis of the cause of bleeding. Patients with newly developed bleeding symptoms should be examined for acquired coagulation disorders. The clinical sings in combination with the special coagulation tests allow the correct diagnosis.