Hematology/Myeloma/Oncology; Types, Evaluation, Treatment

Types of Hematology

Myeloid

Hemoglobinopathies (congenital abnormality of the hemoglobin molecule or of the rate of hemoglobin synthesis)

• Sickle-cell disease
• Thalassemia
• Methemoglobinemia

Anemias (lack of red blood cells or hemoglobin)

• Iron deficiency anemia
• Megaloblastic anemia
  • Vitamin B₁₂ deficiency
    • Pernicious anemia
  • Folate deficiency

Hemolytic anemias (destruction of red blood cells)

• Genetic disorders of RBC membrane
  • Hereditary spherocytosis
  • Hereditary elliptocytosis
  • Congenital dyserythropoietic anemia
• Genetic disorders of RBC metabolism
  • Glucose-6-phosphate dehydrogenase deficiency (G6PD)
  • Pyruvate kinase deficiency

Immune mediated hemolytic anemia (direct Coombs test is positive)

• Autoimmune hemolytic anemia
  • Warm antibody autoimmune hemolytic anemia
    • Idiopathic
    • Systemic lupus erythematosus (SLE)
    • Evans’ syndrome (antiplatelet antibodies and hemolytic antibodies)
  • Cold autoimmune hemolytic anemia
    • Cold agglutinin disease
    • Paroxysmal cold hemoglobinuria (rare)
    • Infectious mononucleosis

Alloimmune hemolytic anemia

• Hemolytic disease of the newborn (HDN)
  • Rh disease (Rh D)
  • ABO hemolytic disease of the newborn
  • Anti-Kell hemolytic disease of the newborn
  • Rhesus c hemolytic disease of the newborn
  • Rhesus E hemolytic disease of the newborn
  • Other blood group incompatibility (RhC, Rhe, Kid, Duffy, MN, P and others)

• Drug induced immune mediated hemolytic anemia
  • Penicillin (high dose)
  • Methyldopa

• Hemoglobinopathies (where these is an unstable or crystalline hemoglobin)
• Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood cell surface proteins)
• Direct physical damage to RBCs
  • Microangiopathic hemolytic anemia
  • Secondary to artificial heart valve(s)

• Aplastic anemia
  • Fanconi anemia
  • Diamond-Blackfan anemia (inherited pure red cell aplasia)
  • Acquired pure red cell aplasia

Decreased numbers of cells

• Myelodysplastic syndrome
• Myelofibrosis
• Neutropenia (decrease in the number of neutrophils)
• Agranulocytosis
• Glanzmann’s thrombasthenia
• Thrombocytopenia (decrease in the number of platelets)
  • Idiopathic thrombocytopenic purpura (ITP)
  • Thrombotic thrombocytopenic purpura (TTP)
  • Heparin-induced thrombocytopenia (HIT)

Myeloproliferative disorders (Increased numbers of cells)

• Polycythemia vera (increase in the number of cells in general)
• Erythrocytosis (increase in the number of red blood cells)
• Leukocytosis (increase in the number of white blood cells)
• Thrombocytosis (increase in the number of platelets)
• Myeloproliferative disorder

Coagulopathies (disorders of bleeding and coagulation)

• Thrombocytosis
• Recurrent thrombosis
• Disseminated intravascular coagulation
• Disorders of clotting proteins

Hemophilia

• Hemophilia A
• Hemophilia B (also known as Christmas disease)
• Hemophilia C

• Von Willebrand disease
• Disseminated intravascular coagulation
• Protein S deficiency
• Antiphospholipid syndrome

Disorders of platelets

• Thrombocytopenia
• Glanzmann’s thrombasthenia
• Wiskott-Aldrich syndrome

Hematological malignancies

Hematological malignancies

• Lymphomas
  • Hodgkin’s disease
  • Non-Hodgkin’s lymphoma {includes the next five entries}
    • Burkitt’s lymphoma
    • Anaplastic large cell lymphoma
    • Splenic marginal zone lymphoma
    • Hepatosplenic T-cell lymphoma
    • Angioimmunoblastic T-cell lymphoma (AILT)
• Myelomas
  • Multiple myeloma
  • Waldenström macroglobulinemia
  • Plasmacytoma

Leukemias increased WBC

• Acute lymphocytic leukemia (ALL)
• Chronic lymphocytic leukemia (CLL){now included in theCLL/SCLL type NHL}
• Acute myelogenous leukemia (AML)
• Chronic Idiopathic Myelofibrosis (MF)
• Chronic myelogenous leukemia (CML)
• T-cell prolymphocytic leukemia (T-PLL)
• B-cell prolymphocytic leukemia (B-PLL)
• Chronic neutrophilic leukemia (CNL)
• Hairy cell leukemia (HCL)
• T-cell large granular lymphocyte leukemia (T-LGL)
• Aggressive NK-cell leukemia

Miscellaneous

• Hemochromatosis
• Asplenia
• Hypersplenism
  • Gaucher’s disease
• Monoclonal gammopathy of undetermined significance
• Hemophagocytic lymphohistiocytosis
• Tempi syndrome

Hematological changes secondary to non-hematological disorders

• Anemia of chronic disease
• Infectious mononucleosis
• AIDS
• Malaria
• Leishmaniasis

Blood

• Venous blood
• Venipuncture
• Hematopoiesis
• Blood tests
• Cord blood

Red blood cells

• Erythropoiesis
• Erythropoietin
• Iron metabolism
• Hemoglobin
• Glycolysis
• Pentose phosphate pathway

• White blood cells
• Platelets
• Reticuloendothelial system
  • Bone marrow
  • Spleen
  • Liver

Lymphatic system

Blood transfusion

• Blood plasma
• Blood bank
• Blood donors
• Blood groups

Hemostasis

• Coagulation
• Vitamin K

• Complement system
• Immunoglobulins

(abnormality of the hemoglobin molecule or of the rate of hemoglobin synthesis)

• Anemias (lack of red blood cells or hemoglobin)
• Hematological malignancies
• Coagulopathies (disorders of bleeding and coagulation)
• Sickle Cell Anemia
• Thalassemia

Evaluation

A 27 year-old male with sickle cell disease (HbSC) on hydroxurea and with a history of 2-3 hospitalizations per year for vaso-occlusive pain crises manifested by arthralgias and back pain presents to the emergency department with 3 days of worsening joint pain affecting his entire body but predominantly his knees and lower back. He is familiar with this pain and attempted therapy at home with ibuprofen, then hydrocodone-acetaminophen, and finally hydromorphone without improvement and presented to the emergency department.

On review of systems, he denied chest pain, cough, or shortness of breath. He has some periumbilical abdominal pain but tolerated normal oral intake on the day of presentation without vomiting nor changes in bowel habits. He otherwise denied fevers, peripheral numbness/weakness, urinary or fecal incontinence or retention. He similarly denies trauma, weight loss, night sweats, or intravenous drug use.

Objectively, the patient’s vital signs were normal and he was well-appearing. Mucous membranes were moist and skin turgor was normal. There were no appreciable joint effusions, warmth, nor limitation to active/passive range of motion of any joints. His back had no midline tenderness to palpation or percussion, normal range of motion in all axes and extremity sensation and strength testing were normal. Abdominal and genitourinary examinations were normal. The patient had preserved perineal sensation to light touch and normal rectal tone – a core temperature was obtained which was also normal.

Peripheral access was established and a parenteral dose of hydromorphone equivalent to his home oral dose was administered (0.015mg/kg). Repeat dosing was required at 15 minutes due to persistent pain scale of 10. Diphenhydramine and acetaminophen were also administered, for potential opioid-sparing effects, recognizing the limited evidence to support these relatively benign adjuncts.

Laboratory studies were notable for anemia (though stable compared to baseline measures), appropriate reticulocyte count, no evidence of hemolysis and with normal electrolytes and renal function.

A thorough history and examination did not identify a critical precipitant for the patient’s symptoms which were presumed to be secondary to a vaso-occlusive pain crisis. On reassessment, the patient’s pain was improved and an oral dose of hydromorphone was administered with continued observation and serial reassessments for two hours thereafter. The patient’s hematologist was available for follow-up the subsequent morning and the patient was discharged home.

Pharmacokinetics of Commonly-Used Opiate Analgesics

Algorithm for the Evaluation and Management of Sickle Cell Crises

Hematologic Emergencies ,Sickle Cell Crises