Send help...my papercut turned into a major bleed
What type of genetic disorders are hemophilia A & B?
(Ex: dominant vs recessive, x-linked vs autosomal)
X-linked recessive disorders
What is the most common inherited bleeding disorder?
von Willebrand Disease
A 58-year-old male presents with hypotension, fever, and AKI 18 hours after a blood transfusion. What is his diagnosis and how is it treated?
Acute Hemolytic Transfusion Reaction
- most cases result from clerical error resulting in ABO incompatibility
- stop transfusion and check for incompatibility and hemolysis
- initiate fluid resuscitation, vasopressor support, and mannitol
Please list the CRAB findings in multiple myeloma.
C: Hypercalcemia
R: Renal Insufficiency
A: Anemia (look for rouleaux formation)
B: Bone lesions - lytic lesions
What is the gene and chromosome associated with CML?
- bcr-abl gene and t(9:22) Philadelphia chromosome
- chronic phase usually the presenting phase and lasts many years, WBC > 20, presence of a left shift without elevation in lymphocytes or monocytes, and splenomegaly
- acclerated phase has less differentiation with the presence of 10-20% blasts
- terminal blast phase has > 20% blasts and is associated with acute leukemia
An 18-year-old woman has prolonged bleeding following a tooth extraction. She also has long periods. She is otherwise healthy. Physical examination is unremarkable. CBC is normal. The aPTT is prolonged and corrects with a mixing study. Platelet Function Analyzer closure time is prolonged. Factor VIII activity is 60% of normal. Which of the following is the most likely diagnosis?
A. Factor VIII inhibitor
B. Hemophilia A
C. Vitamin K Deficiency
D. von Willebrand Disease
D. von Willebrand Disease
- autosomal dominant with variable penetrance
- results in mild to moderate bleeding in the form of epistaxis, heavy menstrual flow, and bleeding during surgery or trauma
- screen with prolonged platelet function analyzer closure time or normal or prolonged aPTT
- definitive diagnostic tests include vWF antigen level and activity assay which will be low, Factor VIII level which may be low, or von Willebrand multimer which will be elevated
What are two indications for fresh frozen plasma administration?
- Warfarin reversal in actively bleeding patients where PCC is not available
- Thrombotic Thrombocytopenia purpura
- Dilutional coagulopathy during massive transfusion
- Bleeding with multiple factor deficiencies (DIC or liver disease)
A 45-year-old G3P2 female presents with anemia, jaundice, and fever 7 days after a PRBC transfusion. What is her diagnosis and how is it treated?
Delayed Hemolytic Transfusion Reaction
- an anamnestic response to minor red cell antigens that occurs 5-10 days after erythrocyte transfusion
- seen commonly in frequently transfused patients or history of pregnancy
- repeat type and screen to identify a new alloantibody
- treatment is supportive
List 4 tests that you would order for the workup of multiple myeloma.
CBC and serum chemistries
SPEP, 24 hour UPEP
Serum and urine immunofixation assays
Serum free light chain testing
Serum IgG, IgA, and IgM
Skeletal survey (plain x-ray radiographs)
A 58-year-old asymptomatic man has a leukocyte count of 55,000. Hemoglobin and platelet counts are normal. The spleen is palpable. A peripheral blood smear shows an increased number of granulocytic cells in all phases of development. Cytogenetic testing reveals a Philadelphia chromosome. Which of the following is the best management?
A. Allogenic stem cell transplantation
B. Hydroxyurea
C. Imatinib
D. Observation
E. Plasmapheresis
C. Imatinib (tyrosine kinase inhibitor) eradicates the Philadelphia chromosome and achieves clinical remission in chronic phase CML
- Hydroxyurea is for palliation only and decreases leukocytosis and splenomegaly
- Allogenic stem cell transplantation is a potential cure for patients with good performance status and refractory disease as well as a potential cure for selected patients in the accelerated phase or blast phase
A 30-year-old male presents with recurrent hemarthroses. PT is normal but aPTT is prolonged. aPTT corrects with mixing study. What is the diagnosis?
Hemophilia
- treat with recombinant factor VIII and IX
- give desmopressin for mild hemophilia A
What are the three indications for a platelet transfusion?
- platelets < 10,000 in most patients
- platelets 50,000-100,000 in patients undergoing surgery or actively bleeding
- platelets < 100,000 in patients undergoing CNS surgery or CNS bleeding
A 58-year-old woman develops dyspnea and fever during transfusion of 1 unit of packed erythrocytes. Temperature is 102 F, BP is 116/68 mm Hg, HR is 111/min, and RR is 22/min. Oxygen saturation is 86% on ambient air. There is no JVD or S3. BNP is normal. There are bilateral infiltrates on CXR. Which of the following is the most likely diagnosis?
A. Acute hemolytic transfusion reaction
B. Transfusion related acute lung injury
C. Transfusion related allergic reaction
D. Transfusion related sepsis
Transfusion related acute lung injury (TRALI)
- symptoms occur during or within 6 hours of transfusion in absence of volume overload
- most common cause of transfusion related death
- have antibodies in donor plasma directed against recipient neutrophil antigen which lead to pulmonary leukocyte sequestration and capillary leak leading to noncardiogenic pulmonary edema
- treatment is supportive
A 47-year-old woman with newly diagnosed multiple myeloma is evaluated in the office. Which of the following will be most effective in reducing her risk of having a skeletal related event?
A. Alendronate
B. Calcium and Vitamin D supplementation
C. Prophylactic radiation therapy
D. Zoledronic acid
D. Zoledronic acid
Complications of Multiple Myeloma
- treat pathologic fractures with radiation therapy or surgery
- zoledronic acid reduces skeletal-related events, improves survival even in the absence of bone disease
- treat spinal cord compression with glucocorticoids and radiation therapy
- treat recurrent bacterial infections with immunoglobulin infusion
A 45 year-old-female presents with erythomelalgia, headaches, and blurry vision. Platelets are 650,000. Physical exam reveals livedo reticularis and splenomegaly. What is her diagnosis?
Essential Thrombocythemia
- treat with emergent platelet apheresis for either bleeding or thrombosis (MI, CVA, TIA)
- patients who are asymptomatic but are high risk (platelets > 1,000,000, Age > 60, Cardiovascular risk factors, and previous thrombosis) should be treated with hydroxyurea and ASA
- asymptomatic low-risk patients should be treated with observation or low dose ASA
A 75-year-old woman has a 1 week history of hematuria, epistaxis, and bruising. She has no prior bleeding history. Hgb is 8 g/dL. The PT is normal. The aPTT is 85 s. Following a mixing study the aPTT is 55 s.
Which of the following is the most likely diagnosis?
A. Acquired hemophilia
B. Hemophilia A
C. Hemophilia B
D. Vitamin K deficiency
E. von Willebrand disease
A. Acquired hemophilia
- diagnosed with the presence of a prolonged aPTT that does not correct with a mixing study indicating the presence of an inhibitor
- have an acquired antibody to factor VIII
- causes include idiopathic (50%), postpartum, malignancy, and autoimmune
- treat low inhibitor titers with desmopressin or factor VIII concentrate
- treat high inhibitor titers with active prothrombin complex or recombinant human factor VIIa concentrate
- can use prednisone and cyclophosphamide for long term inhibitor control
What is the treatment for von Willebrand Disease?
- treat with DDAVP before minor invasive procedures or Factor VIII or vWF concentrates for more severe bleeding
A 78-year-old female present with significant dyspnea and hypertension 10 hours following a blood transfusion. HR is 120/min. JVD and S3 are present. What is the diagnosis and how is it treated?
Transfusion Associated Circulatory Overload (TACO)
- pulmonary edema secondary to volume excess or circulatory overload
- occurs in patients who receive a large volume of transfused product over a short period of time
- treat with diuresis and supplemental oxygen
What is the difference between multiple myeloma, smoldering multiple myeloma, and MGUS?
- serum and urine monoclonal protein > 3 g in multiple myeloma and smoldering myeloma but < 3 g in MGUS
- bone marrow clonal plasma cells > 10% in multiple myeloma and smoldering multiple myeloma but less < 10% in MGUS
- end-organ damage is present in multiple myeloma and not smoldering multiple myeloma or MGUS
Name two causes of secondary erythrocytosis.
- Hypoxemia
- Diuretics
- Anabolic steroid use
- Kidney or liver carcinoma
What blood product should you refrain from using in von Willebrand Disease?
Cryoprecipitate increases the infection risk
What does cryoprecipitate consist of and when should it be used?
- consists of von Willebrand factor, Factor VIII, Factor XIII, Fibronectin, and Fibrinogen
- should be used in patients with hypofibrinogenemia from liver disease, thrombolytic therapy, and DIC
A 67-year-old male presents with a maculopapular rash, abdominal pain, and diarrhea following an allogenic hematopoietic cell transplant. Hgb is 6, WBC is 1.5, and platelets are 12,000. AST and ALT are in the 400's. What is his diagnosis?
Transfusion-Associated Graft vs Host Disease
- fatal transfusion complication
- occurs during engraftment of donor lymphocytes into the recipient
- prevent with gamma irradiation of cellular products
Name the induction chemotherapy treatment for multiple myeloma.
- Bortezomib (proteasome inhibitor)
- Thalidomide or Lenalidomide (an immunomodulatory agent)
- Prednisone or Dexamethasone (a glucocorticoid)
-Melphalan or Cyclophosphamide (an alkylating agent)
- Autologous HSCT is indicated in select patients following induction
How do you diagnose and treat polycythemia vera?
- diagnose with the presence of JAK2V617F mutation (present in 97%) and splenomegaly
- treat with phlebotomy for a target hematocrit to < 45% and low dose ASA
- patients at high risk for thrombosis (age > 60, previous thrombosis, cardiovascular disease) should be treated with hydroxyurea as well