• Aggregation
• Antibody
• Heparin-induced thrombocytopenia
• Immune thrombosis
• Platelet activation
• Vaccine-induced thrombotic thrombocytopenia

• Pregnancy
• Female
• Humans
• Postpartum Hemorrhage/diagnosis
• Postpartum Hemorrhage/etiology
• Postpartum Hemorrhage/therapy
• Blood Coagulation Disorders/complications
• Blood Coagulation Disorders/diagnosis
• Blood Coagulation Disorders/therapy
• Disseminated Intravascular Coagulation/diagnosis
• Disseminated Intravascular Coagulation/etiology
• Disseminated Intravascular Coagulation/therapy

We here report a 21-year-old male who presented with acute myelomonocytic leukemia (AMML) associated with acquired von Willebrand syndrome (AVWS). To our knowledge, this is the first case of AVWS caused by AMML. In our case, following remission-induction chemotherapy combined with idarubicin and cytarabine, the patient showed remarkable improvement of bleeding symptoms due to AVWS. Moreover, after an allogeneic stem cell transplantation from a sibling donor, both AMML and AVWS maintain complete remission.

• Acquired von Willebrand syndrome
• Acute myeloid leukemia
• Bleeding disorders
• Coagulation
• Haemostasis

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.

• aggregometry
• aspirin
• clopidogrel
• platelet aggregation
• platelet function disorders
• tailored antiplatelet therapy
• thienopyridines

The European Clinical Laboratory and Molecular (ECLM) criteria define 10 distinct Willebrand diseases (VWD): recessive type 3, severe 1, 2C and 2N; dominant VWD type 1 secretion/clearance defect, 2A, 2B, 2E, 2M and 2D; and mild type 1 VWD (usually carriers of recessive VWD). Recessive severe 1 and 2C VWD are characterized by secretion and multimerization defects caused by mutations in the D1-D2 domain. Recessive 2N VWD is a mild hemophilia due to D’-FVIII-von Willebrand factor (VWF) binding site mutations. Dominant 2E VWD caused by heterozygous missense mutations in the D3 domain is featured by a secretion-clearance-multimerization VWF defect. Dominant VWD type 2M due to loss of function mutations in the A1 domain is characterized by decreased ristocetin-induced platelet aggregation and VWF:RCo, normal VWF multimers and VWF:CB, a poor response of VWF:RCo and good response of VWF:CB to desmopressin (DDAVP). Dominant VWD type 2A induced by heterozygous mutations in the A2 domain results in hypersensitivity of VWF for proteolysis by ADAMTS13 into VWF degradation products, resulting in loss of large VWF multimers with triplet structure of each individual VWF band. Dominant VWD type 2B due to a gain of function mutation in the A1 domain is featured by spontaneous interaction between platelet glycoprotein Ib (GPIb) and mutated VWF A1 followed by increased proteolysis with loss of large VWF multimers and presence of each VWF band. A new category of dominant VWD type 1 secretion or clearance defect due to mutations in the D3 domain or D4-C1-C5 domains consists of two groups: Those with normal or smeary pattern of VWF multimers.

• Von Willebrand disease
• Von Willebrand factor
• ADAMTS13
• DDAVP
• Von Willebrand factor assays
• Von Willebrand gene mutations

• ADAMTS13
• DDAVP
• von Willebrand disease
• von Willebrand factor
• von Willebrand factor assays
• von Willebrand factor multimers
• von Willebrand factor mutations

• anti-inflammatory treatment
• blood transfusion
• plasma exchange
• thrombotic thrombocytopenic purpura

• 1‐desamino‐8‐d‐arginine vasopressin
• congenital von Willebrand disease
• multiple myeloma
• preoperative screening
• prolonged apTT
• von Willebrand factor

• Gene mutations
• NGS
• molecular biology methods
• von Willebrand disease
• von Willebrand factor

Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

• bleeding
• mechanical circulatory support
• thrombosis
• von Willebrand factor

We recently developed a longer lasting recombinant factor VIII-Fc fusion protein, rFVIIIFc, to extend the half-life of replacement FVIII for the treatment of people with hemophilia A. In order to elucidate the biological mechanism for the elongated half-life of rFVIIIFc at a cellular level we delineated the roles of VWF and the tissue-specific expression of the neonatal Fc receptor (FcRn) in the biodistribution, clearance and cycling of rFVIIIFc. We find the tissue biodistribution is similar for rFVIIIFc and rFVIII and that liver is the major clearance organ for both molecules. VWF reduces the clearance and the initial liver uptake of rFVIIIFc. Pharmacokinetic studies in FcRn chimeric mice show that FcRn expressed in somatic cells (hepatocytes or liver sinusoidal endothelial cells) mediates the decreased clearance of rFVIIIFc, but FcRn in hematopoietic cells (Kupffer cells) does not affect clearance. Immunohistochemical studies show that when rFVIII or rFVIIIFc is in dynamic equilibrium binding with VWF, they mostly co localize with VWF in Kupffer cells and macrophages, confirming a major role for liver macrophages in the internalization and clearance of the VWF-FVIII complex. In the absence of VWF a clear difference in cellular localization of VWF-free rFVIII and rFVIIIFc is observed and neither molecule is detected in Kupffer cells. Instead, rFVIII is observed in hepatocytes, indicating that free rFVIII is cleared by hepatocytes, while rFVIIIFc is observed as a diffuse liver sinusoidal staining, suggesting recycling of free-rFVIIIFc out of hepatocytes. These studies reveal two parallel linked clearance pathways, with a dominant pathway in which both rFVIIIFc and rFVIII complexed with VWF are cleared mainly by Kupffer cells without FcRn cycling. In contrast, the free fraction of rFVIII or rFVIIIFc unbound by VWF enters hepatocytes, where FcRn reduces the degradation and clearance of rFVIIIFc relative to rFVIII by cycling rFVIIIFc back to the liver sinusoid and into circulation, enabling the elongated half-life of rFVIIIFc.

• Animals
• Factor VIII/metabolism
• Hepatocytes/metabolism
• Histocompatibility Antigens Class I/physiology
• Mice
• Mice, Knockout
• Receptors, Fc/physiology
• Receptors, Scavenger/metabolism
• Recombinant Fusion Proteins/metabolism
• Tissue Distribution
• von Willebrand Factor/metabolism

In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered.

• bleeding
• laboratory assessment
• method
• platelets
• point-of-care testing
• thrombosis

In the event of blood vessel damage, human platelets are promptly recruited on the site of injury and, after their adhesion, activation and aggregation, prevent blood loss with the formation of a clot. The consequence of abnormal regulation can be either hemorrhage or the development of thrombosis. Qualitative and/or quantitative defects in platelets promote bleeding, whereas the residual reactivity of platelets, despite antiplatelet therapies, play an important role in promoting arterial thrombotic complications. Platelet function is traditionally assessed to investigate the origin of a bleeding syndrome, to predict the risk of bleeding prior surgery or during pregnancy or to monitor the efficacy of antiplatelet therapy in thrombotic syndromes that, now, can be considered a new discipline. “Old” platelet function laboratory tests such as the evaluation of bleeding time and the platelet aggregation analysis in platelet-rich plasma are traditionally utilized to aid in the diagnosis and management of patients with platelet and hemostatic disorders and used as diagnostic tools both in bleeding and thrombotic diathesis in specialized laboratories. Now, new and renewed automated systems have been introduced to provide a simple, rapid assessment of platelet function including point of care methods. These new methodologies are also suitable for being used in non-specialized laboratories and in critical area for assessing platelet function in whole blood without the requirement of sample processing. Some of these methods are also beginning to be incorporated into routine clinical use and can be utilized as not only as first panel for the diagnosis of platelet dysfunction, but also for monitoring anti-platelet therapy and to potentially assess risk of both bleeding and/or thrombosis.

• Platelets
• Method
• Test
• Point of care testing
• Laboratory assessment
• Bleeding
• Thrombosis
• Platelet function

• Antibodies, Monoclonal
• Enzyme-Linked Immunosorbent Assay/methods
• Humans
• Receptors, GABA-B/metabolism
• Reproducibility of Results
• von Willebrand Diseases/diagnosis
• von Willebrand Factor/analysis