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Bleeding Risks With Cardiac Disease

Most of the hematologic complications that occur in cardiac disease are linked to the disturbances in the dynamics of flow. Although there are fewer hemorrhagic complications due to intrinsic cardiac disease than occur with cardiac surgeries and implantation devices, those that do occur are linked to the same pathophysiologies that are seen in the operating rooms and the cath labs. Cardiac Disease Cardiac disease can result…

Bleeding Risks With Vitamin K Deficiency

Introduction In 1894, the condition known as hemorrhagic disease of the newborn was first discovered to be related to a deficiency of vitamin K (VK), which is an essential cofactor for the synthesis of clotting factors, FII, FVII, FIX, FX, as well as the endogenous inhibitors of coagulation, proteins C and S in the liver. Deficiency of VK can lead to a quick decline in the…

Hemostasis in Liver Disease

Liver disease is associated with multiple hemostatic defects leading to both hemorrhagic and thrombotic manifestations. Its effect on coagulation factors, endogenous anticoagulants, and platelets results in rebalanced hemostasis and creates challenging clinical scenarios requiring careful management. Decreased Synthesis of Pro- and Anticoagulant Factors All coagulation factors (except FVIII and von Willebrand factor [VWF]) are synthesized in hepatocytes and can be deficient in chronic liver disease. FVIII…

Vascular Bleeding Disorders

Hereditary Vascular Malformations Hereditary Hemorrhagic Telangiectasia (Osler–Weber–Rendu Disease) Hereditary hemorrhagic telangiectasia (HHT) is a systemic autosomal dominant (AD) vascular disease that is characterized by mucocutaneous telangiectasias and multiple arteriovenous malformations (AVMs). It is the most common inherited vascular bleeding disorder with an estimated incidence of 1 in 5000–10,000 people and affects all ages, races, and sexes equally. There are three identified pathologic gene variants that cause…

Bleeding Disorders in Pregnancy

Postpartum hemorrhage (PPH) is a leading cause of maternal death worldwide. Although the majority of PPH occurs as a result of uterine atony or other anatomical defect, the risk is increased when a congenital or acquired hemostatic defect is present. PPH can be categorized as primary, if there is abnormal bleeding during the first 24 hours (>500 or >1000 mL following vaginal or Caesarean delivery, respectively,…

Factor XIII, α 2 -Antiplasmin, and Plasminogen Activator Inhibitor-1 Deficiencies

Factor XIII (FXIII), α 2 -antiplasmin (α 2 -AP), and plasminogen activator inhibitor type 1 (PAI-1) deficiencies are all very rare bleeding disorders. These proteins play a critical role in stabilizing a fibrin clot (FXIII) and regulating fibrinolysis through the inhibition of plasmin (α 2 -AP) or the inhibition of plasminogen conversion to plasmin (PAI-1). FXIII affects 1 in 2 to 3 million individuals worldwide; the…

Congenital Disorders of Fibrinogen

Congenital fibrinogen disorders include a spectrum of defects that fall into two categories: quantitative (type I) and qualitative (type II) fibrinogen disorders. Quantitative (type I) disorders include the absence of fibrinogen (afibrinogenemia) or low fibrinogen activity and antigen levels typically <150 mg/dL (hypofibrinogenemia). Qualitative (type II) disorders entail low fibrinogen activity but discordant normal antigen (dysfibrinogenemia) or reduced antigen (hypodysfibrinogenemia). The incidence of afibrinogenemia is estimated…

Factor II, Factor V, and Factor X Deficiencies

Introduction Inherited deficiencies of factors II, V, and X (FII, FV, and FX) are rare (estimated frequencies are FII, 1 in 2,000,000; FV, 1 in 1,000,000; and FX, 1 in 1,000,000). Patients who are homozygous or compound heterozygous for defects in the F2, F5 , or F10 genes can have moderate to severe bleeding symptoms, with patients who have FX deficiency being more likely to manifest…

Factor VII Deficiency

Factor VII (FVII) deficiency is the most common autosomal recessive rare bleeding disorder. It was first described in 1951 and has an estimated prevalence of 1 in 500,000. The manifestation of bleeding symptoms in FVII deficiency is clinically heterogeneous. Some individuals with FVII deficiency may have mild symptoms, whereas others may have severe and potentially life-threatening bleeding symptoms. Moreover, a proportion of patients remain asymptomatic. Even…

Factor XI Deficiency

Factor XI (FXI) deficiency, was first described in 1953. It is characterized by a highly variable bleeding phenotype. Some patients have no apparent excessive bleeding while others have more substantial bleeding. In contrast to other coagulation factor deficiencies, excessive bleeding in FXI deficiency is also highly variable in an individual patient, who might hemorrhage after one hemostatic challenge but not after another. Homozygotes or compound heterozygotes…

Hemophilia B

Hemophilia B, also known as Christmas disease, results from a congenital deficiency or absence of coagulation factor IX (FIX). It is an X-linked recessive disorder with an incidence of approximately 1:25,000 live male births and accounts for 15%–20% of hemophilia cases. It is thought to affect around 3300 patients in the United States. The term “Christmas disease” comes from Stephen Christmas, who was the first patient…

Hemophilia A

Hemophilia A (also known as classical hemophilia) results from congenital deficiency of factor VIII (FVIII). It is an X-linked recessive disorder that results in decreased or absent circulating FVIII activity, leading to lifelong bleeding tendency. Hemophilia A has an incidence of approximately 1:5000 male births and accounts for approximately 85% of cases of hemophilia. It affects all racial and ethnic groups equally. Pathophysiology FVIII is a…

von Willebrand Disease

von Willebrand disease (VWD) is the most common hereditary bleeding disorder affecting as much as 1% of the general population. The VWF (von Willebrand factor) protein has three essential hemostatic functions: (1) binding to FVIII thereby prolonging its half-life, (2) binding to collagen in the underlying subendothelial matrix, and (3) binding to platelets; thus, VWF recruits platelets to the injury site by functioning as a bridge…

Antiphospholipid Syndrome

Introduction The antiphospholipid (aPL) syndrome (APS) is an autoimmune thrombophilic condition that is defined by a combination of clinical and laboratory criteria. In general terms, APS patients have developed circulating antibodies against plasma proteins that bind to phospholipids (i.e., aPL antibodies) with subsequent clinical morbidity of thrombosis and/or pregnancy complications. The investigational criteria for APS (often referred to as the Sydney Investigational Criteria) are detailed in…

Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a syndrome consisting of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and end-organ damage secondary to microvascular thrombi. Anemia, thrombocytopenia, fever, neurological signs, and renal dysfunction makeup the classic pentad; however, TTP can present without the full pentad; up to 35% of patients do not have neurological signs at presentation, and renal abnormalities and fever are not prominent features. TTP should be suspected…

Hemolytic Uremic Syndrome

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). This disease can be divided into three major subtypes: typical HUS, atypical HUS (aHUS), and DEAP-HUS (deficiency of CFHR plasma proteins and autoantibody positive HUS). Typical HUS makes up the majority of cases in children (90%) and is associated with bloody diarrhea caused…

Autoimmune Lymphoproliferative Syndrome

Introduction Autoimmune lymphoproliferative syndrome (ALPS) was first described in 1967 when Canale and Smith reported on five children with massive lymphadenopathy and splenomegaly mimicking lymphoma. In 1992 Sneller et al. similarly described two patients with a progressive lymphoproliferative disorder associated with autoimmunity and whose blood and lymph nodes demonstrated an increase in an atypical population of CD41992 − and CD8 − T cells (double-negative T cells, DNTs).…

Heparin-Induced Thrombocytopenia

Epidemiology The reported incidence of heparin-induced thrombocytopenia (HIT) after heparin exposure is 0.2%–7%, though the accuracy of such estimates is limited by the challenges of disease recognition and diagnosis. Risk factors may be host- or heparin-related. Heparin-Related Risk Factors The most important heparin-related risk factors are type of heparin formulation and length of exposure. Among heparin formulations, the incidence is lower with smaller, less charged species.…

Drug-Induced Thrombocytopenia

Introduction Drug-induced thrombocytopenia (DIT) is a common clinical problem, and numerous drugs have been implicated in the development of thrombocytopenia. The risk of thrombocytopenia after any drug is low, and only a small number of patients taking a suspected medication will develop the problem. However, many patients who develop DIT are taking multiple medications and are critically ill, making the diagnosis difficult. Rapid recognition of thrombocytopenia…

Chronic Immune Thrombocytopenia

Introduction Immune thrombocytopenia (ITP) is a bleeding disorder characterized by immune-mediated platelet destruction with resultant thrombocytopenia and mucocutaneous bleeding. Chronic ITP is defined by ITP persistence beyond 12 months, with spontaneous recovery occurring in less than 10% of adults. The estimated incidence of ITP is ∼100 cases per 1 million persons per year, with about half in adults. Approximately twice as many women are affected as…