Evaluation of Patients Bleeding Disorders
Patients with bleeding disorders present with symptoms of
easy bruising, bleeding gums, menorrhagia, gastrointestinal bleeding, or postoperative bleeding.
This pathology is a X-linked hereditary bleeding disorders primarily found in male patients. Daughters of men with this disease are obligate carriers. They present in a similar fashion, with spontaneous hemarthrosis or bleeding into deep muscles or with excessive or delayed bleeding after trauma. Small cuts do not usually bleed excessively, but patients experience mucocutaneous bleeding.
Hemophilia A and B
Bleeding in patients with liver disease results from one of many interrelated hemostatic aberrations. The liver is the site of production for procoagulant and fibrinolytic factors. Liver disease is associated with bleeding and thrombosis.
Asymptomatic patients do not require treatment, but ___________________ should be considered if the INR is elevated.
vitamin K supplementation
Distinguishing between liver disease and disseminated intravascular coagulation may be challenging.
Measuring what factors can separate the 2 disorders in theory?
Measuring factor VIII levels (not affected by liver disease) and factor V levels (not consumed during intravascular coagulation) provides a theoretical means of separating the two disorders
Although measuring levels of factor VIII (normal in liver disease) and factor V (not consumed during intravascular coagulation) could theoretically distinguish coagulopathy of liver disease from disseminated intravascular coagulation, patients may have components of both disorders, and the management is usually analogous regardless of this distinction.
Primary hemostasis describes the interaction between
platelets, von Willebrand factor (vWF), and the vessel wall
This symptom involves bleeding into joints, often seen in hemophilia .
Hemarthrosis
Condition of articular bleeding, that is into the joint cavity. This can occur after an injury or, more commonly, in bleeding disorders such as hemophilia. Patients will typically present with pain, swelling and a decreased range of motion of the involved joint.
The coagulation cascade was first fully described in this century.
20th century
Active bleeding in patients with coagulopathy of liver disease should be managed with
cryoprecipitate to maintain fibrinogen levels greater than 100 mg/dL (1 g/L) and platelet transfusions to achieve a platelet count greater than 75,000/µL (75 × 109/L).
Disseminated intravascular coagulation results from the simultaneous stimulation of
coagulation and fibrinolysis.
It is associated with severe sepsis, usually with septic shock; with disseminated malignancy, most classically with mucin-secreting pancreatic adenocarcinoma; and in pregnancy with various severe complications, including sepsis, placental abruption, and eclampsia.
Secondary hemostasis refers to
the activation of coagulation factors that eventually lead to fibrin clot formation. Clots are then degraded through fibrinolysis.
What antifibrinolytic medication helps reduce bleeding?
Tranexamic acid
The most common hereditary bleeding disorder, is caused by either deficiency or ineffectiveness of
Von Willebrand disease (vWD),vWF deficiency leads to mucocutaneous bleeding symptoms that mimic thrombocytopenia.
This pathology occurs in conditions of high circulatory shear stress like valvular heart disease, hypertrophic cardiomyopathy, circulatory assist devices, and extracorporeal membrane-oxygenation systems caused by excessive degradation of high-molecular-weight von Willebrand multimers by the proteolytic enzyme ADAMTS13
Acquired von Willebrand Disease
Affected patients develop bleeding conditions similar to those in hereditary vWD.
The prevalence of this disorder is likely to increase as more patients with severe cardiomyopathy are managed with left ventricular assist devices. These patients are routinely managed with warfarin and antiplatelet agents and have a significant incidence of gastrointestinal or other bleeding problems. Desmopressin and vWF concentrates have been used in management
Classic laboratory findings of disseminated intravascular coagulation
include thrombocytopenia, prolonged activated partial thromboplastin and prothrombin times, elevated INR, hypofibrinogenemia, and elevated D-dimer levels.
This drug stimulates release of preformed von Willebrand factor and factor VIII, is used to treat minor bleeding in most patients with von Willebrand disease and is given prophylactically before surgery or procedures
Desmopressin
Differential Diagnoses
Prolonged PT, normal aPTT
Differential Diagnoses
Factor VII deficiency
DIC
Liver disease
Vitamin K deficiency
Warfarin ingestion
The scientist who was the first patient identified to have hemophilia B?
In 1952, Stephen Christmas, then a five-year-old boy, was diagnosed with a bleeding disorder that wasn't the previously known type of hemophilia (hemophilia A, or factor VIII deficiency). Researchers, Rosemary Biggs and Robert Gwyn Macfarlane, found that he lacked clotting factor IX, a different protein from the one missing in classic hemophilia.
Daily requirement of this vitamin comes from gut microflora (which may be destroyed by antibiotics); absorption requires biliary and pancreatic function
It acts as a cofactor for carboxylation and activation of certain coagulation factors & for the endogenous anticoagulants, protein C, and protein S.
Vitamin K
What organ produces most of the body’s clotting factors?
Liver
Patients with life-threatening illnesses characterized by systemic immune response syndrome with hypotension and multiorgan dysfunction are at risk for this pathology.
Disseminated Intravascular Coagulation
Normal PT, prolonged aPTT
Deficiency of factors VIII, IX, XI, or XII
von Willebrand disease (if severe and factor VIII level is quite low)
Heparin exposure
Hereditary vWD is subclassified into 3 broad groups, with type 1 being the most common.
Desmopressin is ineffective in patients with type 3 vWD. What is the medical management for these patients?
Von Willebrand factor concentrates are used for major bleeding and to treat patients with rare subtypes 2B and 3.
Cryoprecipitate is no longer used because virally inactivated vWF concentrates are safer and more effective.
Acquired _______________results from an autoantibody directed against factor VIII. Patients present with bleeding symptoms that mimic _____________.Approximately half of all cases are associated with pregnancy and the postpartum state, malignancy, and other autoimmune disorders, as well as with medications.
Acquired Hemophilia
Hereditary hemophilia A.
Which coagulation factors are vitamin K-dependent?
Factors II, VII, IX, X, and proteins C and S
This device measures the ability of platelets to occlude the aperture and reports the closure time. The biologic stimuli and the high shear rates generated by the standardized flow result in platelet attachment, activation, and aggregation; therefore, the system theoretically can detect defects at any stage of platelet function.
The Platelet Function Analyzer-100 (PFA-100®)
Measures platelet function under flow conditions that create a high shear, similar to flow through the blood vessel. Whole blood passes through an aperture cut into a membrane coated with collagen and either epinephrine or ADP.