1 N5315 Advanced Pathophysiology Disorders of Hemostasis Coagulopathy versus Thrombocytopenia A coagulopathy is a defect in the coagulation process which results in the prolongation of the PT and/or PTT. In most instances the individual with a coagulopathy will be at an increased risk of bleeding. In some instances (this is rare), there is no increased risk of bleeding. This is the case when an individual has a deficiency of Hageman Factor (Factor XII). Bleeding which occurs as a result of a coagulopathy manifests differently than a bleed which results from a thrombocytopenia. Clinical manifestations of a bleed from a coagulopathy include: • joint bleeding • tissue hematomas • large, spontaneous, centrally located ecchymosis • bleeding after trauma, surgery or an injury tends to be delayed A thrombocytopenia is a decrease in the total number of platelets. This has numerous etiologies. Bleeding which occurs as a result of a thrombocytopenia manifests differently than a bleed which results from a coagulopathy. Clinical manifestations of a bleed from a thrombocytopenia include: • Mucosal bleeding such as: • Epistaxis • Oral bleeding • GI or GU bleeding (in the absences of malignancy) • Hemoptysis • Heavy menses • Bleeding occurs immediately after a trauma or injury • Petechiae may be present. The differences in the clinical manifestations of a coagulopathy and a thrombocytopenia should be used to help you identify the defect and determine the etiology of the bleed. These clinical manifestations, as do any clinical manifestations, help to guide your evaluation and management of the patients for which you provide care.2 Alterations of Platelets Thrombocythemia and thrombocytosis both indicate that there is an increased number of platelets. This can occur due to bone marrow disorders or after a splenectomy. The spleen stores some platelets and after it is resected the individual will have a higher platelet count. Thrombocytopenia is the term used to describe a low number of platelets. The risk of bleeding from a thrombocytopenia is directly associated to its severity. In most instances a platelet count above 50,000 is enough to maintain hemostasis. As platelets drop below that level the individual begins to have some signs of bleeding. The most severe scenario occurs when the count is less than 10,000. At this level the person can have spontaneous bleeds. The most worrisome would be an intracranial bleed. Be familiar with the parameters you have seen on your slide. • Risk of bleeding • Platelet counts >50,000: adequate for hemostasis in most instances • Platelet counts 30,000-50,000: these individuals will rarely develop purpura even with trauma • Platelet counts 10,000-30,000: These individuals are usually asymptomatic but are at risk for excessive bleeding with trauma • Platelet counts of < 10,000: Experience spontaneous bleeding and display petechiae General rules as they apply to Thrombocytopenia • A Platelet count >50,000 is usually indicated for invasive procedures. • A Platelet count of above 80,000 to 100,000 is required by most surgeons and anesthesiologists for surgery. Common causes of thrombocytopenia include: • Hemodilution which tends to occur post-operatively and has a nadir of 2-4 days. A nadir refers to the lowest point. • Splenomegaly which is seen in some cancer patients and patients with cirrhosis. The spleen sequesters platelets. • HIV, bone marrow failure • Hemolysis • Medications cause a lot of issues and thrombocytopenia is one of them. On this slide you see a list of medications which can cause thrombocytopenia. • Sulfonamides • Vancomycin • Quinine –remember tonic water • Linezolid (Zyvox)3 • Heparin • Abciximab (Reopro) • Eptifibatide (Integrilin) • Tirofibab (Aggrastat) • Rifampin (Rifadin) • Piperacillin • Beta Lactam antibiotics (PCN, Cephalosporins) • Valporic acid (Depakote) • Carbamazepine (Tegretol) • Phenytoin (Dilantin) Primary Immune Thrombocytopenic Purpura is also known as idiopathic thrombocytopenic purpura. It is an acquired thrombocytopenia which results from an immune mediated destruction of the platelets. There is a secondary form of ITP and in this instance there is an etiology identified for the cause of ITP. Primary ITP refers to an isolated thrombocytopenia in the absence of another etiology such as SLE, CML, Antiphospholipid syndrome, or medications. It is not a very common disorder. It occurs more commonly in women. Children tend to experience an acute form of ITP which resolves in 1-2 months. Acute ITP is usually secondary to viral infections, SLE, or drug allergies. Chronic ITP tends to be idiopathic in nature (or primary) and is progressive. Etiologies for secondary ITP include: • Preceding viral infection: HIV, VZV, CMV, HCV • Disease states (as above) cause secondary ITP Process of platelet destruction begins with the phagocytosis of platelets by macrophages. The macrophages then present the digested platelet peptides to the CD4 cells. The CD4 cells believe these peptides are antigens and initiate the immune response. IgG antibodies then bind to platelets most often on the platelet membrane glycoproteins such as GPIIb/IIIa and ultimately platelets are destroyed. Neonatal thrombocytopenia may occur because of a mother with ITP being pregnant. The IgG antibodies cross the placenta, coat the fetus’ platelets and potentially cause platelet destruction. An alloimmune response from a mother without ITP may occur and cause intrauterine thrombocytopenia. When the fetus’ platelet count drops below 20,000, there is a high risk of intracranial hemorrhage. Clinical manifestations of ITP include:4 • Presentation can vary • Petechiae, purpura, and easy bruising are expected. • Epistaxis, gingival bleeding, and menorrhagia are common. • Overt gastrointestinal bleeding and gross hematuria are rare. • Intracranial hemorrhage, a potentially fatal bleeding complication, is so uncommon that there is no reliable estimate of its frequency. • The clinical manifestations of thrombocytopenia also vary with age. Older patients may have more severe bleeding manifestations, such as gastrointestinal bleeding and possibly intracranial hemorrhage because of comorbidities such as hypertension. Thrombotic Thrombocytopenic Purpura (TTP) Characteristically TTP results in severe
View Full Document
Unlocking...