Obliterující vaskulopatie v dermatologii představují heterogenní skupinu onemocnění s rozdílnou patogenezí. Jedná se o stavy nezánětlivého uzávěru cévního lumen s následně navozenou ischemií tkáně (kůže). V současné nomenklatuře se setkáváme i s termínem kožní mikrovaskulární okluzivní syndromy, který lépe charakterizuje postižení kožních cév. Onemocnění, která jsou odpověděná za okluzivní syndromy představují patologie trombocytů, přítomnost kryoglobulinů, infekce postihující cévní stěnu, embolizace (např. cholesterolu), koagulopatie (antifosfolipidový syndrom), nebo onemocnění doprovázející chronické selhání ledvin (kalcifylaxe). Mezi možné kožní projevy patří ulcerace, nekrotické léze, livedo racemosa a retiformní purpura. Práce poskytuje ucelený pohled na složitou problematiku těchto stavů a poukazuje na kožní projevy, které jsou v rutinní praxi považovány za projevy vaskulitid.
Obliterative vasculopathies in dermatology represent a heterogeneous group of diseases with different pathogenesis. These are conditions of non-inflammatory occlusion of the vascular lumen with subsequently induced ischemia of the tissue (skin). In the current nomenclature, we also encounter the term cutaneous microvascular occlusive syndromes, which better characterize the involvement of skin vessels. Diseases that are responsible for occlusive syndromes include platelet pathology, the presence of cryoglobulins, infections affecting the vessel wall, embolisation (e.g. cholesterol), coagulopathy (antiphospholipid syndrome), or diseases accompanying chronic kidney failure (calciphylaxis). Possible skin manifestations include ulceration, necrotic lesions, livedo racemosa, and retiform purpura. The work provides a comprehensive view of the complex issue of these conditions and points to skin manifestations that are considered as manifestations of vasculitis in routine practice.
- Keywords
- obliterující vaskulopatie,
- MeSH
- Embolism, Cholesterol pathology therapy MeSH
- Diagnosis, Differential MeSH
- Blood Coagulation Disorders classification complications MeSH
- Skin Diseases, Vascular * classification pathology MeSH
- Skin Manifestations MeSH
- Cryoglobulinemia pathology therapy MeSH
- Humans MeSH
- Blood Platelet Disorders diagnosis classification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Examination Questions MeSH
Krvácivé stavy představují situace, které se klinicky projevují krvácením nebo jeho zvýšeným rizikem. Důvodů je celá řada. Vedle anatomických příčin patří mezi hlavní důvody hemoragie porucha hemostázy. Z klinického pohledu jde o situace, kdy je krvácení neúměrné vyvolávajícímu podnětu nebo vzniká spontánně, mohou se také projevovat obtížně stavitelným nebo protrahovaným krvácením po operaci nebo poranění. Podkladem je narušení rovnováhy v důsledku kvantitativní či kvalitativní poruchy některého z hemostatických mechanismů, příčiny se mohou i kombinovat. Cílem příspěvku je poskytnout, ve vymezeném rozsahu, přehled těchto stavů se zdůrazněním aspektů využitelných v běžné klinické praxi.
bleeding disorders are situations manifested clinically by bleeding or an increased risk of bleeding caused by various reasons. In addition to anatomical causes, the main reasons for haemorrhage include impaired haemostasis. From the clinical point of view these are clinical situations in which bleeding is inadequate to inducing stimulus or begins spontaneously and may manifested itself as difficult-to-stop bleeding or prolonged bleeding after operation or after injury. The basis is disturbance of balance due to a quantitative or qualitative disturbance of one of the hemostatic mechanisms, the causes can be combined. The aim of this article is to provide an overview of these conditions in defined scope, highlighting aspects useful in routine clinical practice.
- MeSH
- Disseminated Intravascular Coagulation diagnosis physiopathology therapy MeSH
- Hemophilia A diagnosis physiopathology therapy MeSH
- Homeostasis MeSH
- Hemorrhage * diagnosis etiology therapy MeSH
- Humans MeSH
- Blood Platelet Disorders diagnosis physiopathology therapy MeSH
- Purpura, Thrombotic Thrombocytopenic diagnosis physiopathology therapy MeSH
- von Willebrand Diseases diagnosis physiopathology therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Blood Coagulation Disorders, Inherited genetics classification pathology therapy MeSH
- Blood Coagulation Factors analysis classification MeSH
- Blood Coagulation Disorders * diagnosis classification pathology therapy MeSH
- Humans MeSH
- Risk Factors MeSH
- Blood Platelet Disorders diagnosis etiology drug therapy classification MeSH
- Thrombocytopenia diagnosis etiology drug therapy classification MeSH
- Thrombophilia etiology drug therapy MeSH
- von Willebrand Diseases diagnosis drug therapy classification MeSH
- Blood Coagulation Tests classification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) support is often associated with bleeding complications caused by secondary or primary hemostasis pathology. However, there are limited data investigating primary hemostasis using Multiplate aggregometry with specific diagnostics tests for vWF (von Willebrand factor) deficiency. AIMS: The aim of this study was to find out whether short-term ECMO produces the pathology of primary hemostasis that is detected by Multiplate aggregometry and to investigate the pathology of vWF. METHODS: In this study, blood samples of 20 patients undergoing lung transplantations with short-term perioperative ECMO support were analyzed. The multimeric structure, the levels of von Willebrand factor antigen (vWF), ristocetin cofactor (RCo), collagen-binding protein (CB), and the results of multiple electrode aggregometry RISTO (ristocetin), ADP (adenosine diphosphate), ASPI (Aspirin®; arachidonic acid), and TRAP (thrombin receptor activating peptide) tests were compared to the samples obtained before and after ECMO support. RESULTS: The Multiplate ADP and RISTO tests showed the presence of significant pathology in primary hemostasis after surgery (p < 0.05), suggesting the presence of acquired platelet dysfunction. Although the RISTO tests suggest the presence of acquired vWF deficiency, laboratory tests for vWF antigen and RCo and CB tests showed an increase in this case. The multimeric structure of vWF did not show clinically significant deterioration. CONCLUSIONS: Multiple aggregometry ADP, ASPI, and TRAP tests seem to be able to detect primary hemostasis pathology (platelets aggregation and adhesion pathology) that is present during short-term perioperative ECMO support in lung transplantation procedures. Interestingly, RISTO tests seem to be more suitable for the diagnosis of platelet dysfunction than the diagnosis of acquired vWF deficiency in this situation.
- MeSH
- Adenosine Diphosphate MeSH
- Hemostasis MeSH
- Humans MeSH
- Extracorporeal Membrane Oxygenation * adverse effects methods MeSH
- Retrospective Studies MeSH
- Blood Platelet Disorders * MeSH
- von Willebrand Diseases * MeSH
- von Willebrand Factor metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.
- MeSH
- Blood Proteins genetics MeSH
- Hemorrhage MeSH
- Humans MeSH
- Blood Platelet Disorders * diagnosis genetics MeSH
- Platelet Function Tests MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Hemoragická nemoc novorozence se projevuje neočekáváným krvácením většinou u jinak zcela zdravých novorozenců a kojenců a je způsobena nedostatkem vitaminu K, který vede ke snížené aktivitě vitamin K dependentních koagulačních faktorů. Příčinou je nízký obsah vitaminu K v mateřském mléce a nedostatečná syntéza vitaminu K střevní flórou novorozence. Existují tři formy tohoto onemocnění: časná (0–24 hodin), klasická (2.–7. den) a pozdní (2.–12. týden). Pro časnou a pozdní formu je typické riziko závažného intrakraniálního krvácení s až 50% mortalitou u pozdní formy. Diagnostickým standardem je vyšetření protrombinového času, který je minimálně čtyřnásobně prodloužen při normální hladině trombocytů a fibrinogenu. Léčbou již rozvinutého onemocnění je vitamin K, popřípadě čerstvě zmražená plazma (u dětí optimálně HVLP Octaplas®). Od šedesátých let 20. století je celosvětově zavedeno profylaktické podání vitaminu K novorozencům. V rámci diferenciální diagnostiky je u novorozenců s intrakraniálním krvácením vždy nezbytné vyloučit úraz, vrozené poruchy krevního srážení, jako je hemofilie, ale také trombocytopatii či trombocytopenii.
Hemorrhagic disease of a newborn is manifested by unexpected bleeding mostly in otherwise healthy newborns and infants and is caused by vitamin K deficiency, which leads to insufficient activity of vitamin K-dependent coagulation factors. The cause is the low level of vitamin K in breast milk and the insufficient synthesis of vitamin K by the neonatal bifid intestinal microflora. There are three forms of this disease, early-onset (0-24 hours), classic (2-7 days) and late-onset (2-12 weeks). Risk of severe intracranial bleeding is typical for the early and late forms, with up to 50% mortality in the late form. The diagnostic standard is the examination of the prothrombin time greater than 4 times the normal values in the presence of a normal level of platelets and fibrinogen. The treatment of an already developed disease is vitamin K, in severe cases also fresh frozen plasma (in children optimally Octaplas®). Since the sixties of the 20th century, the prophylactic administration of vitamin K has been recommended worldwide. As a part of the differential diagnosis in newborns with intracranial bleeding, it is always necessary to rule out trauma, hereditary bleeding disorders such as hemophilia, but also thrombocytopathy or thrombocytopenia.
- MeSH
- Vitamin K Deficiency Bleeding * diagnosis drug therapy MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Vitamin K therapeutic use MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Review MeSH
The calcium release activated calcium channel is activated by the endoplasmic reticulum-resident calcium sensor protein STIM1. On activation, STIM1 C terminus changes from an inactive, tight to an active, extended conformation. A coiled-coil clamp involving the CC1 and CC3 domains is essential in controlling STIM1 activation, with CC1 as the key entity. The nuclear magnetic resonance-derived solution structure of the CC1 domain represents a three-helix bundle stabilized by interhelical contacts, which are absent in the Stormorken disease-related STIM1 R304W mutant. Two interhelical sites between the CC1α1 and CC1α2 helices are key in controlling STIM1 activation, affecting the balance between tight and extended conformations. Nuclear magnetic resonance-directed mutations within these interhelical interactions restore the physiological, store-dependent activation behavior of the gain-of-function STIM1 R304W mutant. This study reveals the functional impact of interhelical interactions within the CC1 domain for modifying the CC1-CC3 clamp strength to control the activation of STIM1.
- MeSH
- Erythrocytes, Abnormal MeSH
- Dyslexia genetics MeSH
- HEK293 Cells MeSH
- Ichthyosis genetics MeSH
- Calcium Release Activated Calcium Channels metabolism MeSH
- Cloning, Molecular MeSH
- Nucleic Acid Conformation MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy MeSH
- Patch-Clamp Techniques MeSH
- Migraine Disorders genetics MeSH
- Miosis genetics MeSH
- Models, Molecular MeSH
- Mutation genetics MeSH
- Neoplasm Proteins genetics MeSH
- ORAI1 Protein genetics MeSH
- Stromal Interaction Molecule 1 genetics MeSH
- Spleen abnormalities MeSH
- Muscle Fatigue genetics MeSH
- Blood Platelet Disorders genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Pembrolizumab patří mezi inhibitory imunitních kontrolních bodů protinádorové imunity (immune checkpoint inhibitors). Porucha funkce štítné žlázy představuje častý nežádoucí účinek této léčby. Autoři předkládají kazuistiku pacienta léčeného pembrolizumabem pro nemalobuněčný karcinom plic, u nějž došlo po přechodné fázi subklinické hypertyreózy k poměrně rychlému rozvoji těžké hypotyreózy - a v té době i ke spontánnímu vzniku rozsáhlých podkožních hematomů. V rámci hematologické diferenciální diagnostiky byly cíleně vyloučeny: von Willebrandův syndrom, získaná hemofilie A, dysfibrinogenemie, aktivovaná fibrinolýza a trombocytopatie. Současně byly vyloučeny laboratorní projevy přidruženého autoimunitního onemocnění a myozitidy. Po intenzifikaci substituční terapie levothyroxinem nebyly navzdory pokračování léčby pembrolizumabem zaznamenány nové krvácivé komplikace. Souvislost podkožních hematomů s těžkou polékovou hypotyreózou se nabízí per exclusionem.
Pembrolizumab belongs to so called immune checkpoint inhibitors. Frequent adverse event of this therapy is hypothyroidism. The authors present a case report of patient treated with pembrolizumab for non-small cell lung carcinoma, in whom severe hypothyroidism followed quite rapidly after transient phase of subclinical hyperthyroidism - at this time point new and spontaneous onset of large subcutaneous hematomas was observed. Acquired von Willebrand syndrome, acquired hemophilia A, dysfibrinogenemia, activation of fibrinolysis and thrombocytopathy were all actively ruled out in hematological differential diagnosis. Concomittantly, laboratory markers of secondary autoimmune disease and myositis were excluded. Despite continuous pembrolizumab treatment, there were no other bleeding complications seen after intensification of endocrine substitution therapy with thyroid hormones. Causal relationship between subcutaneous hematomas and severe drug-induced hypothyroidism is established per exclusionem.
- Keywords
- pembrolizumab,
- MeSH
- Hematoma chemically induced etiology MeSH
- Antibodies, Monoclonal, Humanized adverse effects MeSH
- Hypothyroidism * chemically induced MeSH
- Humans MeSH
- Lung Neoplasms drug therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Antineoplastic Agents, Immunological * adverse effects MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
Chronickou lymfocytární leukemii provází dysfunkce imunitního systému. Nerovnováha imunity se mimo jiné projevuje zvýšeným výskytem autoimunitních cytopenií. Pro volbu správného terapeutického postupu je důležité zhodnotit diferenciálně diagnosticky i jiné příčiny anemie, trombocytopenie či granulocytopenie. V terapii se uplatňují zejména kortikosteroidy, intravenózní imunoglobuliny, rituximab, případně další imunosupresiva. Nedostatečná odpověď na terapii je indikací pro zahájení léčby chronické lymfocytární leukemie.
Chronic lymphocytic leukemia is accompanied by dysfunction of the immune system. Immune dysbalances are manifested, among other things, in an increased incidence of autoimmune cytopenias. In order to choose the right therapeutic procedure, it is important to differentially diagnose other causes of anemia, thrombocytopenia or granulocytopenia. Corticoids, intravenous immunoglobulins, rituximab, or other immunosuppressants are mainly used in therapy. Inadequate response to therapy is an indication to initiate treatment for chronic lymphocytic leukemia.
- MeSH
- Humans MeSH
- Blood Platelet Disorders * genetics metabolism MeSH
- Blood Platelets MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
