Hematology II

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<p>Prepared by:</p> <p> Redha Al-Rumaih Ayman Abdulali Sadiq Radhi Ahmad Obidan Ahmed M. Shammasi Abdullah Al- Bat'hi Special thanks to Husain Al-Hashim</p> <p>This note contains what we could catch during the lectures. We tried our best to avoid any mistake that is out of our responsibility if presents. Please contact us if you find mentionable mistake and help modifying this note</p> <p>Hematology White blood cells diseases: o Leukocytosis: Neutrophilia Eosinophilia Basophlia Lymphocytosis Monocytosis o Leucopenia: Granulocytopenia (agranulocytosis) Lymphopenia (infectious mononucleosis) o Tumors: Leukemia: Lymphocytic : o Acute o Chronic Granulocytic: o Acute o Chronic Multiple myeloma. Lymphomas: Hodgkin's lymphoma Non-Hodgkin's lymphoma Platelet Disorders: o Quantitative: Thrombocytopenia Idiopathic thrombocytopenic purpura o Qualitative: Glanzmann's disease Brenard-Soulier Syndrome Coagulation disorders: o Inheretid: Hemophilia Factor disease (Christens disease) von Willebrand disease (lupus anticoagulant) o aquired: vitamin K deficiency. Hepatocellular failure. Disseminated intravascular coagulation (DIC) Deficiency of natural anticoagulants. Myeloprolifirative disorders: o Polycythemia Vera. o Essential Thrombocythemia. o Essential Agogenic Myelofibrosis. o Chronic Granulocytic Leukemia. Blood transfusion: o Packed RBCs. o Platelets o plasma</p> <p>1</p> <p>White blood cell diseases White blood cells (WBCs) are either: o Granulocytic: Neutrophils, Eosinophils, and basophils o Mononuclear: lymphocytes and monocytes. Variations in WBCs count and morphology indicate certain disease conditions. Normal WBCs count is 4,000-10,000/L. Leukocytosis occurs when WBCs count is more than 10,000/L Leukopenia occurs when WBCs count is less than 4,000/L Most of the variations in total leukocyte count are due to or in neutrophils or lymphocytes because they constitute the majority of WBCs.</p> <p>Leukocytosisa- Neutrophilia (neutrophil leukocytosis): Increase neutrophil count. Neutrophil nucleus has 3-4 lobes. If &gt; 4, hypersegmented neutrophil as in megaloplastic anemia. If &lt; 3, hyposegmented ( hypogranular ) seen in preleukemia causes: a. Infection by pyogenic bacteria as in pneumonia. NB. Some infections cause neutropenia b. Physiological as in pregnancy and in newborns. c. Acute hemolytic conditions and active bleeding d. Burns (as it causes inflammation) e. Trauma e.g. surgery f. Hepatic amebiasis (amebic hepatitis): the only parasitic condition causing neutrophilia. g. Myeloprolifirative disorders e.g. polycythemia vera, essential thrombocythemia, and myelofibrosis h. Chronic granulocytic leukemia i. Leukemoid reaction: high WBCs count mistaken for leukemia. Total WBCs count Basophils Leukocyte alkaline phosphatase (LAP)* Philadelphia chromosome* released by neutrophils</p> <p>Chronic granulocytic leukemia &gt; 100,000/L or absent ++</p> <p>Leukemoid reaction 50,000/L Normal -</p> <p>b- Eosinophilia: Increased eosinophil count . Eosinophil has golden yellow granules and a nucleus with 2-3 lobes. o Allergy o Parasitic infection: intestinal worms, liver flukes, bilharziasis, onchocerciasis, tinea worms (and all other tape worms) NB. Malaria and ameba don't cause eosinophilia o Certain malignancies e.g. Hodgkin's lymphoma. o Idiopathic e.g. hypereosinophilic syndrome: charectarized by severe weakness and joint pain. Treated by high doses of corticosteroid.</p> <p>2</p> <p>c- Basophilia Increased basophile count.. Normaly, basophils present in low level (1-2% of WBC count) Causes of basophilia: o Chronic granulocytic leukemia o Myeloproliferative disorders. d- Lymphocytosis: Increased lymphocytes count Causes: o Viral infection. o Chronic lymphocytic leukemia (occurs in adults but never in children). o Non-Hodgkin's lymphoma. o Whooping cough: in children only (its the only acute bacterial infection associated with lymphocytosis. Caused by Bordetella pertussis) Differentiation between Chronic lymphocytic leukemia and whooping cough is by the clinical pattern: age of the patient and the presence or absence of whoops. e- Monocytosis: Causes: o TB. o Chronic infections in general. o Viral infection ( slight increase)</p> <p>Leukopeniaa- granulocytopenia( neutropenia): Agranulocytosis: severe reduction of neutrophil count (&lt; 500/ L) o Leads to body defenses infections Ulcers in the mouth and throat Causes of granulocytopenia: o Aplastic anemia. o Drugs: chloramphenicol, analgesics (e.g. phenylbutazone and butazolidin), sulphonamide, hyperthyroidism drugs, rheumatoid arthritis drugs, chemotherapeutic agents. o Infection: typhoid fever, visceral leishmaniasis, and some viral infection (hepatitis). o Acute leukemia (due to infiltration of bone marrow by malignant cells). b- lymphopenia: Causes : o HIV infection ( destruction of CD4 cells) o Hodgkin's lymphoma. o Infectious mononucleosis.</p> <p>3</p> <p>Infecious mobonucleosis ( glandular fever) Caused by Epstein- Bar virus (EBV) infection which is transmitted by droplet infection and kissing. Affects children and young adults. Patients present with : o Fever, headache, sore throat, feeling ill. o Enlargement of lymph nodes (esp. cervical L.N.s) o Skin rash in the upper abdomen. o Slight enlargement of spleen and/or liver. o Rupture of spleen (as it becomes fragile). Laboratory findings: o Normal Hb level or slight anemia. o Leukocytosis mainly due to lymphocytosis and slight monocytosis. o level of atypical mononuclear cell : reactive T-cell larger than normal lymphocytes with basophilic cytoplasm and nuclear/cytoplasmic ratio. They indicate viral infection in general but its high level indicates this infection. o Normal platelet count. But, patients might develop autoantibodies against red blood cells or platelets leading to immune hemolytic anemia or immune thrombocytopenia, respectively. Evans syndrome is caused by presence of autoantibodies against both red blood cells and platelets, hence, both immune hemolytic anemia and immune thrombocytopenia result. Detection of infectious mononucleosis : o Paul-Bunnell test (heterophile antibody test) : Addition of patients serum to sheep red blood cells result in agglutination because it contains antibodies that agglutinate red blood cells of sheep (or other species)(Heterophile antibodies) o Monospot test: similar test that does not require sheep red cells and use strips containing antigen that agglutinate with the same antibodies. Management: o There is no specific treatment. o Patients are managed by analgesics (palliative treatment), resting, and fluids till the body eradicates the virus.</p> <p>4</p> <p>LeukemiaDefinition: Malignant proliferation of bone marrow cells. Classified according to type of cells into lymphocytic or myeloid (granulocytic) leukemia. And each is further classified into acute and chronic. Acute leukemia</p> <p>a- Acute lymphocytic leukemia (ALL): Disease of children (3-10 yaers old) but can occur in adults. Cells of origin are lymphoblasts: immature lymphocytes. These cells proliferate in bone marrow and involve other organs such as lymph nodes and spleen leading to enlargement of both. Proliferation of the born marrow suppresses its cells resulting in pancytopenia as the infiltration involves the whole marrow. Clinical presentation : (indicate failure of the bone marrow) o Anemia, bleeding and recurrent acute infections. o Bone pain by compression of bone nerves by the malignant cells. o Lymphadenopathy. o Splenomegally. Classification of ALL: o FAB* classification: according to morphology of lymphoblasts. L1 Cell size Nuclear/cytoplasmic ratio Cytoplasm Nucleolus Prognosis Small High Scanty Not prominent Best L2 Large heterogeneous Low Prominent Poor L3 Small Low Basophilic &amp; vacuolated In between L1 &amp; L2 , usually not prominent worst</p> <p>o Immunophenotyping classification: According to specific antibodies. Types: o T- cell o B-cell o non B non T o and Null ALL Nucleotidyl transferase is positive in T-cell and Null ALL types. Prognostic indicators: 1. Age: patient younger than 3 or older than 10 years have poor prognosis. 2. Gender: females have better prognosis as malignant cell may reach testis in males where chemotherapeutic agents can not reach and destroy them. 3. WBC count: the higher the count the worse is the prognosis. 4. Subtype: see table 5. Organ involvement: i. malignant cells may infiltrate the brain and proliferate leading to intracranial pressure , poor prognosis.</p> <p>*</p> <p>French Americam British</p> <p>5</p> <p>ii. Liver, spleen and mediastinal lymph node involvement have poor prognosis. 6. Philadelphia chromosomes (described on P.7) are associated with poor prognosis. b- Acute non-lymphocytic leukemia: Usually disease of adults. Worse prognosis than ALL. FAB classification: (M = myeloid) M0 totally undifferentiated. M1 differentiated using cytochemistry. M2 acute myeloblastic leukemia M3 acute promyelocytic leukemia. M4 acute myelomonocytic leukemia. M5 acute monoblastic leukemia M6 Erythroleukemia (Erythroblastic leukemia) M7 megakaryoblastic leukemia M3 acute promyelocytic leukemia : o Promyelocyte is the stage after myeloblast. o Myelobalsts have fewer granules in addition to Auer rods (glycoprotein material) while promyelocyte have many granules and clusters of Auer rods forming fagots. o As promyeloblast rupture, granules and fagots (procoagulant agents) are released and induce coagulation resulting in disseminated intravascular coagulation (DIC) and depletion of coagulation proteins and platelets leading to severe bleeding. M4 and M5 are characterized by severe gum swelling as the leukemic cells infiltrate the gums. M7 characterized by thrombocytopenia as the malignant cells produce immature platelet. Clinical presentation of Acute non-lymphocytic leukemia in general is similar to that of ALL except that there is no lymphadenopathy, in addition to specific characteristics mentioned above for M 3, M4, and M5. Management: 1. supportive measures: i. Blood transfusion to improve Hb level. ii. Platelet transfusion to restore hemostasis. iii. Rehydration with IV solutions. iv. Blood culture and give antibiotics for detection and treatment of infection. v. Treatment of hyperuricemia (e.g allopurinol) NB. High cell proliferation results in high turnover of nucleoprotein and subsequently hyperurecemia (gout). 2. chemotherapy: including i. Induction of remission. Usually using more than one chemotherapeutic agent. Remission: reduce leukocyte count to as much as 6 months). Majority of patients are children. Acute disease occurs in children, preceded by flu-like illness then they show purpra hemorrhage. Adult may also be affected. Clinical picture: o Bleeding, pertaining to primary hemostasis. 15</p> <p>a </p> <p>o Purpura: small spots of bleeding (pin-head size) on the skin and mucus membrane. o Ecchymosis: when purpra spots join with each others. o Sub-conjunctival hemorrhage. o Epistaxis (nasal bleeding) o Rarely, may lead to intracranial hemorrhage. NB: purpura is 2-10 mm in diameter, where ecchymosis is &gt; 10 mm in diamtere Treatment:: o these patients are given the following in order depending on the response: Corticosteroid in high doses. Intravenous immunoglobulins, which may reduce the production of the antibodies against platelets. Splenectomy: removal of the spleen ( where platelets are destroyed) may reduce platelet destruction. Finally, if the patient does not respond to the mentioned treatments, very potent immunosuppressive drugs (e.g. cyclophosphmide) are used to prevent antibody formation.Qualitative platelet disorder</p> <p>a </p> <p>Glanzmann's disease (thrombasthenia) : Inherited autosomal recessive platelet functional disorder. Common in Iraqi gauche, Jordan as well as in gulf area. Characterized by bleeding : epistaxis, GI bleeding, mucous membrane bleeding and purpura. Caused by deficiency of glycoprotein b and a which act as receptors. Diagnosed from birth as bleeding continues after cutting the umbilical cord for long time. Patients should not undergo surgery unless they receive platelet transfusion before, during and after surgery. Lab finding: o Normal platelet count . o Negative platelet aggregation test ( see below) o Failure of clot retraction test.: Normally blood clots on a glass tube then the clot retracts. o Prolonged bleeding time. Treatment: o Blood (platelet) transfusion. o Contraceptive pills are used in females to prevent postpartum hemorrhage. Also, the uterus may be removed to decrease blood loss. b- Brenard-Soulier Syndrome: Autosomal recessive syndrom, less common than Glanzmann's disease. Lab findings: o Defective platelet function. o Slight thrombocytopenia. o Giant platelets. o No response to von Willebrand factor Platelet aggregation test differentiates between Glanzmann's disease and Brenard-Soulier Syndrome : 16</p> <p>o This test is performed using many agents: Platelets of Glanzmann's disease aggregate with Ristocerin but not with ADP (adenine diphosphate) ,epinephrine or collagen while the opposite occurs in the platelets of Brenard-Soulier Syndrome.</p> <p>Coagulation DisordersCoagulation factors are synthesized in the liver. Synthesis of factors II, VII, IX, and X require vitamin K. Diseases of coagulation factor could be inherited or acquired. Generally, in cases of coagulation disorder, bleeding occurs mainly in muscles, joints, and intestine.</p> <p>Inherited disordersThe most important disorders are factor VIII and factor IX disorder. Hemophilia is the term used to describe factor VIII disorder. Sometimes, factor XIII disorder is so-called hemophilia A, while factor IX disorder (or Christmas disease) is called hemophilia B. Hemophilia Factor VIII is a complex molecule consisting of: o Factor VIII clotting activity. o von Willebrand factor (vWF). Hemophiliac patients require medical team consisting of hematologist, psychologist , orthopedic and others as the disease has its impact on many aspects of patients health. Pattern of inheritance: o For factor VIII clotting activity, it is x-linked recessive. Thus, males are mostly affected (disorder of males), while females are almost carriers. o For vWF, it is an autosomal recessive. Clinical Presentation: o Patients usually present with bleeding tendency during childhood. o This bleeding ranges from mild, moderate to severe depending on the degree of the inheritance. o Sites of hemorrhage include: muscles and joints and rarely intracranial hemorrhage. Clinical history: o It is a very important contributor for diagnosis. o Gender: patients are usually males. o Family history: ask about any similar history of bleeding in the maternal uncles and other children in the family suffering from similar symptoms. o History of circumsetion: some patient may present with severe hemorrhage after circumsetion. This bleeding may continue until death. Classification: o Severe: bleeding occurs spontaneously. o Moderate: bleeding after slight trauma. o Mild: patient bleeds excessively when exposed to sur...</p>