Heme / Onc Emergencies

Heme/Onc Emergencies Hanh Truong Dec 19, 2007

A 32-year-old man complains of shortness of breath. He has just started trimethoprim-sulfamethoxazole for chronic sinusitis. He is cyanotic. His pulse oximetry is 85% and does not improve despite 100% oxygen. His lungs are clear. Room air arterial blood gas shows a PaO2 of 94. Appropriate therapy for this patient would be: A. subcutaneous epinephrine 1:1000. B. intravenous diphenhydramine. C. rapid sequence intubation. D. albuterolnebulization. E. intravenous methylene blue

Methemoglobinemia Causes: • Exposure – aniline dyes (shoes), food additives • Medications – lidocaine, sulfonamides, dapsone, benzocaine, pyridium, nitrates/nitrites – not at usual exposure levels • Hereditary deficiencies (methemoglobinreductase) Diagnosis: • MetHb level • ABG: nml PaO2, nml cal O2 sat, low pulse O2 sat • Place venous blood on piece of paper, in normals, should turn bright red after 15 min, MetHb won’t Antidote : methylene blue

Methemoglobinemia

A 35 y.o. female with lupus presents following a seizure. She says that she has not felt well over the past few days but is not taking any medications. VS are normal except for temp 38.3C. Exam is significant for scleraliceterus and multiple area of purpura. The rest of exam is normal. Labs: Na 138, Cl 102, BUN 18, Glucose 90, K .5, HCO3 24, Cr 3.2, WBC 7, Hct 24%, Plt 15K, INR 1.0. Peripheral smear reveals schistocytes, urine pregneg, CT head is normal. Which of the following is the best approach to treatment? • A. Administration of aspirin • B. Administration of heparin • C. Administration of platelets • D. Hemodialysis • E. Plasma exchange

Thrombotic Thrombocytopenic Purpura (TTP) • Pentad: fever, microangiopathichemolysis (elevated LDH), renal failure, CNS dysfunction, and thrombocytopenia • Deficiency/diminished ADAMTS-13 (cleaves vWFmultimers) • Platelet thrombi lead to turbulent blood flow • causing hemolysis (schistocytes and jaundice) • Tissue ischemia (seizure and renal failure) • Tx: emergent plasmapheresis, steroid, splenectomy, vincristine as last resort • Platelet infusion can worsen thrombosis • Triggers includes: Pregnancy, HIV, an autoimmune disorder (lupus)

A 5-year-old girl complains of weakness and fatigue. Two weeks ago she saw her family doctor and was diagnosed with an upper respiratory infection. She received no medicine at that time. Physical examination shows only a scattered petechial rash located in areas where her clothing is snug against her skin, such as underwear elastic lines. Laboratory studies show a white blood cell count 11,000/mm3 , Hgb 10.5 mg/dL, and platelet count of 16,000/mm3. Appropriate management of this patient should be: A. platelet concentrate transfusion. B. discharge home with instructions to limit contact sports. C. admit for salicylate therapy. D. admit for splenectomy. E. admit for observation

Autoimmune Thrombocyopenia (ITP) • Seen in kids, post viral disease • Mucosal or skin bleeding, petechiae, purpura • Spherocytes, not fragmented cells • Platelet usually to less than 20,000/mm3 • Self-limited, > 90% rate of spontaneous remission. • Treatment is supportive, and steroid therapy does not alter the disease course.

A 26 y.o. male with know Hemophilia A presents after being hit in the head with a baseball. PE reveals an abrasion on his forehead and a normal neuro exam. CT head normal. What is the most appropriate management? • A. Administer DDAVP, and discharge pt home • B. Administer factor replacement and admit • C. Admit the patient for observation • D. Check factor IX level, and d/c patient home if they are adequate • E. Discharge the patient home with follow-up

Hemophilia • 85% is hemophilia A = factor VIII deficiency • X-linked recessive, 1 per 1,000 live male births • Females are carriers and have 50% of the normal clotting factor • 60% have severe disease (less than 1% of the normal clotting factor) • Bleeding sites • Joint – destruction with time • Soft tissue – most dangerous about the neck (airway) • Extremities – compartment syndrome

Hemophilia • Bleeding sites (cont) • Mucocutaneous – mouth, GI , nose • CNS – IC bleeds the most common cause of bleeding death – can be spont (c/o HA -treat as bleed before get CT scan) • Genitourinary – hematuria, common but not usually serious • Bone cysts from resolved hematomas • High incidence of HIV (leading cause of death), Hep B & C • Tests – usually normal PT, thrombin clotting time • Abnormal aPTT

Hemophilia - Treatment • Low threshold for factor replacement when any CNS complaints – followed by CT • Major bleeds – bring factor VIII to 80-100% activity level = 50 units/kg • Minor bleeds – 30-50% activity • Watch for bleeding that may compromise the airway • Retroperitoneal bleeding can be a major occult source of bleeding • Watch for compartment syndrome – pain, paresthesias, sensory, motor or vascular defects

Hemophilia – Treatment cont. • Avoid central lines and IM injections prior to factor replacement • Desmopressin (DDAVP): may raise factor VIII levels three-fold in 1 hour (mech unknown) • Can increase level in pts with mild-mod disease and those without inhibitors • Dose = 0.3 ug/kg SC or IV over 30 min • Or nasal spray 150 ug/spray – 2 in adults, 1 in children • Factor VIII concentrate (or FFP and cryoprecipitate if factor not available) • 1 ml FFP = 1 unit of factor (large volume) • 1 ml cryoprecipitate = 6 units of factor VIII (no factor IX) • Recombinant and monoclonal antibody purified products of factor VIII now available

Hemophilia B • Christmas disease • Factor IX deficiency, symptoms similar to A • Prolonged aPTT • Factor IX not present in cryoprecipitate

Which of the following statements regarding von Willebrand disease is correct? A. Bleeding time is normal B. Characterized by inadequate hepatic production of von Willebrand factor C. Most common congential bleeding disorder D. Use of desmopressin is ineffective in controlling bleeding E. Use of vitamin K is indicated to control bleeding

A 38-year-old woman has von Willebrand’s disease, Type I. She complains of blood-tinged emesis and epigastric pain. Her stool tests weakly positive for blood. Appropriate initial therapy includes: A. vitamin K. B. 6 units platelet concentrate. C. factor IX concentrate. D. desmopressin (DDAVP). E. plasmapheresis

Von Willebrand Disease • Most common inherited coagulation disorder • Autosomal dominant; 1 per 100 have some deficiency, but only 1 per 10,000 have a clinical bleeding disorder • Von Willebrand factor allows platelets to adhere to damaged endothelium and it carries factor VIII in the plasma • PT, aPTT, and thrombin clotting times usually normal • Treatment: desmopressin and factor VIII conc.

A 4-year-old boy has fever and headache. Temperature = 104°F, heart rate = 168, respiratory rate = 42, blood pressure = 58/35 mmHg. He is lethargic and irritable, and has a purpuric rash. You start antibiotics and steroids and perform a lumbar puncture, which shows Gram-negative diplococci. One hour later, the nurse notes that there is oozing from his IV site. He then has a large bloody stool and passes dark red-brown urine which tests strongly positive for blood. You expect lab studies to show: A. elevated fibrinogen. B. elevated fibrin degradation products(FDP) and d-dimers. C. diminished INR. D. elevated platelet count. E. shortened thrombin clot time

DIC • Most commonly caused by liberation of tissue activating factor – small fibrin and blood clots deposited in the microcirculation (consume clotting factors: can cause tissue hypoxemia) – fibrinolysis – fibrin degradation products – D-dimer, FDP’s • Causes – meningococcemia (most extreme form of DIC), trauma (especially head – release of brain thromboplastins), sepsis, dead fetus (retained products of conception)

Clinical Manifestations Bleeding Thrombosis Purpura fulminans Gangrene Multisystem organ failure Lab findings Prolonged PT Low platelets Low fibrinogen level Elevated FDP’s and d-dimer Fragmented RBC’s DIC

DIC Treatment • Treat the precipitating factor • If primarily bleeding manifestations, follow the PT (best single test in this setting) • Give FFP replacement if PT prolonged plus vitamin K and folate • If primarily thrombosis – consider low dose heparin infusion (evidence is not strong)

A 72-year-old woman with a past history of congestive heart failure complains of epigastric pain, black bowel movements, and vomiting some “coffee-ground” material. Her hemoglobin is 6.5 mg/dL, so you order two units of packed red blood cells for transfusion. The first unit is transfused uneventfully over a 45 minute period. Thirty minutes after the second unit of packed red blood cells is started, she complains of a headache and shortness of breath. Her lung exam now shows bilateral crackles. You tell the nurse to: A. give a bolus of intravenous saline. B. use a leukocyte reduction filter. C. administer diphenhydramine. D. slow the transfusion and begin diuresis. E. stop the transfusion and report a transfusion reaction

A 72-year-old woman with a past history of congestive heart failure complains of epigastric pain, black bowel movements, and vomiting some “coffee-ground” material. Her hemoglobin is 6.5 mg/dL, so you order two units of packed red blood cells for transfusion. The first unit is transfused uneventfully over a 45 minute period. Thirty minutes after the second unit of packed red blood cells is started, she complains of a headache and shortness of breath. Her lung exam now shows bilateral crackles. You tell the nurse to: A. give a bolus of intravenous saline B. use a leukocyte reduction filter C. administer diphenhydramine D. slow the transfusion and begin diuresis E. stop the transfusion and report a transfusion reaction

Transfusion Complications • Volume Oveload • Recommended rate: 1 unit over 4 hours (patient with low cardiovascular reserve) • Symptoms: headaches and shortness of breath • Signs: congestive heart failure • Treatment: slowing the rate of infusion and diuresis of the patient

Immediate transfusion reaction • Acute hemolytic transfusion reactions • usually ABO incompatibility • RBC’s destroyed by antibodies • Fever, chills, low back pain, breathlessness, burning at infusion site • May progress to hypotension, bleeding, respiratory failure, ATN

Acute hemolytic transfusion reactions • Treatment • Stop transfusion • Hydration to promote brisk diuresis • symptomatic • Lab • Free hemoglobinemia and hemoglobinuria • Haptoglobin (test for free hgb) and indirect bilirubin decreased • Coombs testing of pre- and post-transfusion blood (a test for globulin antibodies on the surface of RBC’s)

Immediate transfusion reaction • Febrile nonhemolytic transfusion reaction • About 1 per 200 units transfused • Fever (at least 1 deg C) and usually chills • Due to interaction between recipient and donor non-RBC components • Usually occurs with multiple transfusions • May be hard to distinguish from early acute hemolytic reaction • Must stop transfusion and r/o acute hemolytic reaction

Immediate transfusion reaction • Allergic transfusion reactions • About 1% of transfusions • Due to plasma protein incompatibilities • Erythema, urticaria, pruritis, bronchospasm, vasomotor instability • Reaction severity is not dose related and discontinuation of transfusion is not always required

A 42-year-old woman with known adult T-cell lymphoma-leukemia complains of back pain, abdominal pain, and confusion. Laboratory evaluation shows a total calcium of 15.8 mg/dl. Appropriate management of this patient should include: A. plasmapheresis. B. IV bicarbonate. C. IV hypertonic saline and oral potassium. D. IV normal saline and IV furosemide. E. glucagon.

Cancer-Related Hypercalcemia • Calcium and albumin • Most calcium bound to albumin • Low serum albumin = low serum calcium • Biologically active calcium is the ionized unbound component • Calcium and phosphate • Multiplied product of both generally = 40 • When one declines, the other goes up • Calcium and pH • Alkalosis causes a decrease in ionized calcium and increase in bound calcium = functional hypocalcemia

Cancer-Related Hypercalcemia • Usual causes – renal cell cancer, multiple myeloma (40% are hypercalcemic), lymphoma, bony mets (lung, breast, prostate) • Suggestive findings – altered sensorium, constipation, hypertension, back pain, QT shortening, polyuria – secondary • Treatment – IV saline and lasix, steroids, phosphate, dialysis, mithramycin

A healthy 12-year-old African-American female complains of weakness and fatigue 3 days after starting a course of trimethoprim-sulfamethoxasole and pyridium for a urinary tract infection. Her hemoglobin is 4.8 mg/dl, and her urine is tea-colored, but you see no red blood cells on microscopic exam. She probably has undiagnosed: • hemolytic uremic syndrome. • G6PD deficiency. • idiopathic thrombocytopenic purpura. • thrombotic thrombocytopenic purpura. • sickle cell disease.

G6PD deficiency • X-linked disorder • Affects 15% of African Amer. males • Precipitated by infection, oxidant drugs, metabolic acidosis, fava beans • Antibiotics: dapsone, nitrofurantoin, phenzopyridine, sulfur containing drugs • Short-live and treatment is supportive

A 54-year-old woman complains of back pain for several months. She now has two days of urine and stool incontinence and ‘numbness’ when she wipes with toilet paper. You suspect spinal cord compression, which: A. commonly occurs as a presenting symptom in a patient with a previously unsuspected malignancy. B. is always associated with back pain, but not tenderness. C. usually responds to aggressive chemotherapy. D. usually causes asymmetric motor or sensory defects. E. can usually be diagnosed by plain radiographs, with CT or MRI adding little.

Cancer-Related Spinal Cord Compression • Most often associated with • Multiple myeloma • Lymphomas • Lung cancer • Prostate cancer • Breast cancer • Causes: bleeding, infection, fracture, tumor mass • Manifestations: chronic lower back pain, neuro deficits, urinary retention, decreased sphincter tone, decreased sensation, LE weakness, difficulty with walking

The anemia in adult sickle-cell disease is due to: A. poor marrow production. B. abnormal protein-binding capacity. C. increased red-cell destruction. D. overactive antibody-antigen response. E. sequestration

Sickle Cell Anemia • Genetically based chronic hemolytic anemia • Baseline hemoglobin = 6-9 g/dl • 5-15% reticulocyte count • Cardiac and respiratory dysfunction is common • Icteric routinely • Splenomegaly – splenic infarction - autosplenectomy

In a patient with sickle-cell disease, infectious crises are primarily due to: A. leukopenia. B. marrow shutdown. C. poor antibody production. D. functional asplenia. E. antibiotic resistance

Heme / Onc Emergencies