Step 3 Hematology I

• It is a common malignancy in patients with advanced HIV infections, and is strongly related to the Epstein-Barr virus (EBV).
• It is usually associated with a significant degree of immunosuppression.
• Most patients with PCNSL have a persistently depressed CD4 count (less than 50/microL).
• Institution of HAART therapy is associated with an improved prognosis, especially in patients who demonstrate an improvement in the immune status (e.g. increase in CD4 count and decrease in viral load), because the degree of immunosuppression seems to be the major determinant of these patients' survival.

• It is a common complication of cancer.
• Some of the common cancers with a tendency to metastasize to the spinal column are prostate, breast, lung, non-Hodgkin's lymphoma, and renal cell carcinoma.
• Clinical Presentation: Classic thoracic radicular pain (wraps around the abdomen) accompanied by weakness and sensory changes in the lower extremities consistent with ESCC.
• The absence of bowel or bladder dysfunction should not dissuade one from the diagnosis since it is typically a late finding.

• Cord compression is a medical emergency and the treatment should be instituted as soon as possible.
• High-dose corticosteroids (especially dexamethasone) should be administered immediately, and MRI of the spine should be obtained to confirm the diagnosis. Corticosteroids exert their effect by decreasing the edema and swelling around the tumor tissue, thereby decreasing the compression.
• Definitive therapy generally consists of radiation therapy for radiosensitive tumors ( Lymphoma, Multiple Myeloma) whereas surgical decompression is used for more radioresistant tumors ( Non Small Cell Lung Cancer).

• It is an episode of acute pain that can range in severity from minimal to agonizing.
• It is the most common type of vasocclusive event in patients with sickle cell disease.
• Although most of these crises have no identifiable cause, events such as dehydration, cold, infection, stress, menses, alcohol consumption, and nocturnal hypoxemia are known triggers.

• Some studies have also shown hemoglobin more than 8.5 g/dl to be a major risk factor for the development of an acute painful episode.
• Various areas of the body can be affected, with the most common locations including the back, chest, extremities, and abdomen.
• Objective clinical signs such as fever or tachypnea are seen approximately half the time.
• The first step in management of patients (especially children) presenting with an acute painful episode is the administration of fluids orally or intravenously to ensure optimal hydration.

• Intravenous Morphine is the most commonly prescribed analgesic in sickle cell patients.
• Another option used (especially in patients stricken with bone pain) is the non-steroidal anti-inflammatory drug ketorolac, which provides pain relief superior to meperidine.
• However, fluid resuscitation should be performed first.

• In SSC, a dramatic fall in hemoglobin concentration occurs secondary to vaso-occlusion within the spleen and splenic pooling of red blood cells.
• Typically the spleen rapidly enlarges, and the patient can go on to experience hypovolemic shock.
• Patients with SSC who do not receive blood transfusions in time have a mortality rate of 10-15%.
• Therefore, a complete blood count should be ordered next for this child with splenomegaly.

• Whole brain radiation therapy is the mainstay of treatment of multiple brain metastases.
• It can improve survival to three to six months.

• Heparin-induced thrombocytopenia should be suspected in patients receiving heparin anticoagulation who have thrombocytopenia, thrombosis (arterial or venous), or a more than 50% drop in the platelet count from baseline 5-10 days after the initiation of treatment.
• Type I HIT occurs due to a nonimmune direct effect of heparin on platelet activation and usually presents within the first 2 days of heparin exposure.
• The platelet count then normalizes with continued heparin therapy and there are no clinical consequences.

• It is a more serious immune-mediated disorder due to antibodies to platelet factor 4 (PF4) complexed with heparin. This leads to platelet aggregation, thrombocytopenia, and thrombosis (both arterial and venous).
• Platelet counts usually drop more than 50% from baseline with a nadir of 30,000-60,000/microL.
• Type 2 HIT usually presents 5-10 days after the initiation of heparin therapy and may lead to life threatening consequences (ie, limb ischemia, stroke).
• The 4Ts score (thrombocytopenia, timing, thrombosis, and other causes) can help assess HIT probability.
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• All forms of heparin (including low-molecular-weight heparin such as enoxaparin) must be stopped immediately in patients with suspected heparin induced thrombocytopenia (HIT) while awaiting diagnostic confirmation.
• Patients with HIT remain at high risk of thrombosis even after discontinuation of heparin.
• Therefore, an alternate, rapidly acting, non-heparin anticoagulant such as direct thrombin inhibitor (eg, argatroban, bivalirudin) must be started immediately.
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• The best way to prevent heparin-induced thrombocytopenia (HIT) is to use low-molecular weight heparin instead of unfractionated heparin whenever possible.
• However, once patients are diagnosed with HIT, they must avoid all forms of heparin (including low molecular-weight heparin) for life.
• This includes heparin flushes for arterial lines and heparin-coated catheters. Information on this "heparin allergy" must be conveyed in the patient's medical record.

• It is a prokinetic agent that acts as a central and peripheral D2-receptor blocker.
• It is used to treat (and prevent) chemotherapy induced emesis; however, its use has been associated with extrapyramidal symptoms.
• The common central nervous system effects include akathisia, dystonia, and parkinsonian-like symptoms.
• Metoclopramide has now been largely replaced by 5 HT3 serotonin receptor antagonists (e.g. ondansetron) and aprepitant.

• At least 80% of the cases of SVCS are due to bronchogenic carcinoma.
• The classic presentation of SVCS begins with dyspnea, persistent cough, facial fullness and neck pain, and progresses into hoarseness, dysphagia, chest pain and syncope.
• Pertinent physical findings are edema and erythema of the neck (which may sometimes compromise the face), and dilated veins of the arms and neck.
• Advanced disease is manifested by cyanosis, collateral veins in the thorax, ocular proptosis and lingual edema.

• The best diagnostic test for SVCS is a contrast CT scan of the chest and neck, which will reveal an obstruction of the superior vena cave due to the pulmonary mass, the metastatic nodes, or an intravenous thrombus.
• CT scan is very useful because it can reveal the extent of obstruction and provide a histopathologic diagnosis (via percutaneous biopsy), which will determine the particular therapeutic regimen required to manage the underlying malignancy.

• As a general rule, for an adult with a body surface area of 2.0 m2, a transfusion of 1 unit of platelets should immediately raise the post-transfusion platelet count by approximately 5,000/microl.
• If there is a smaller than expected rise in the platelet count, refractoriness to platelet transfusions should be considered.

• It is defined as an absolute platelet count increment of less than or equal to 2,000/microl per unit of platelet transfusion given to an average-sized adult.
• Alloimmunization is one of the common and treatable causes of platelet refractoriness.
• It results from the production of antibodies to HLA class 1 antigen on the transfused platelets.
• These alloantibodies can cause a rapid destruction of the transfused platelets and can cause refractoriness to platelet transfusion.
• The post-transfusion platelet count should be measured 10 - 60 minutes after the completion of transfusion.

• Initial treatment with warfarin is contraindicated, as rapidly dropping protein C levels cause a prothrombotic state.
• Warfarin is usually started after the patient is treated with a non-heparin anticoagulant and recovers a platelet count to more than 150,000/microL

• After blood is ordered for transfusion, the following compatibility testing is usually performed. First, the patient's ABO and Rh types are determined. After this, the patient's serum is screened for unexpected antibodies, a procedure called pretransfusion antibody screening.
• Pretransfusion antibody screening is intended to detect any of all clinically significant RBC antibodies.
• If negative, the patient can be safely transfused.
• If positive, further investigation is usually warranted to evaluate the identity of the antibody.
• The major problem that leads to difficulties finding cross-matched blood in patients with a history of multiple transfusions is alloantibodies (e.g., in patients with sickle cell anemia or myelodysplasia). The most commonly implicated RBC antigens in that case are E, L and K. Moreover, these patients tend to develop multiple alloantibodies that make finding compatible blood even more difficult.

• ITP is due to platelet destruction by antiplatelet autoantibodies, which are most often directed against membrane proteins (eg, GPIIb/llla).
• Circulating platelets are rapidly removed by the autoantibodies, limiting the role of platelet transfusions.
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• Immune thrombocytopenic purpura (ITP) is acute and self-limiting in children but usually becomes a chronic disorder in adults.
• Patients with asymptomatic mild thrombocytopenia (platelets more than 30,000/microL without bleeding) can generally be observed without treatment.
• Corticosteroids are a first-line treatment option for patients with symptoms and/or a platelet count of less than 30,000/microL; the majority of adults respond within 1-2 weeks.

• Intravenous immunoglobulin can be considered in patients who have failed or have contraindications to steroid therapy or require a more rapid increase in platelet counts.
• Anti-Rh(D) is an alternate treatment option in rhesus positive non-splenectomized patients.
• Rituximab can be considered for patients who have failed initial treatment.
• Splenectomy is generally reserved for refractory cases.

• Correction of the platelet dysfunction is necessary in patients with active bleeding or those who are about to undergo a surgical procedure.
• Several available options to correct the abnormality include the following: correction of anemia, administration of desmopressin, dialysis, estrogen treatment, and cryoprecipitate infusion.
• Desmopressin represents the simplest and least toxic acute treatment of a prolonged bleeding time.
• It acts by increasing the release of factor Vlll:von Willebrand factor multimers from endothelium.

• LHRH agonist monotherapy is contraindicated in patients with painful vertebral metastases and severe ureteral obstruction.
• These symptoms get worse during the initial testosterone surge seen in the first week of therapy.
• In such cases, an antiandrogen (e.g., flutamide) is given for one week before starting LHRH agonist monotherapy to block the effects of the initial testosterone surge.

• It remains a common clinical problem, despite early detection and treatment of the cancer.
• The most common site of spread is the bones, especially the axial skeleton.
• Skeletal metastases are usually osteoblastic, and should be suspected in a patient with prostate cancer presenting with a new onset or worsening of chronic back pain.
• A radionuclide bone scan is the single most useful imaging modality for assessing any new bony metastasis.

• Androgen depletion is the primary treatment for men with a metastatic prostate cancer.
• It is usually palliative rather than curative, and most patients lose the responsiveness to hormonal manipulations within two years.

• Luteinizing hormone releasing hormone (LHRH) agonists (leuprolide) bind to the LHRH receptors in the anterior pituitary gland and cause an initial release of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which causes a transient rise of testosterone levels.
• After approximately one week of continuous therapy, there is down regulation of LHRH receptors, causing a decrease in the levels of LH. This leads to a significant decrease in the levels of testosterone.
• In the first week of therapy, the patient's symptoms tend to get worse during the initial testosterone surge.

• It is the most common cause of inherited or heredity thrombophilia, accounting for approximately 40-50% of the inherited thrombophilias.
• These disorders predispose the patient to the development of venous thromboembolism.

• It typically develops within an hour after the transfusion is started.
• AHTR is a medical emergency usually caused by ABO incompatibility (possibly due to clerical error) or presence of other antibodies.
• Patients who require chronic red cell transfusions (eg, African American patients with sickle cell anemia) may form multiple antibodies to common Rh, Kell, or other blood group antigens.

• Patients typically present with fever, chills, hemoglobinuria, flank pain, and discomfort at the infusion site.
• This may advance to renal failure (due to immune complex deposition) and disseminated intravascular coagulation (DIC).
• Diagnosis is made by a positive direct Coombs test, pink plasma (plasma free hemoglobin more than 25 mg/dl), hemoglobinuria, and repeat type and cross match showing a mismatch.
• AHTR should be managed by immediately stopping the transfusion and aggressively hydrating the patient with normal saline (not Ringer's or dextrose) to treat the hypotension and prevent renal failure.

• It is the most common adverse reaction that occurs within 1-6 hours of transfusion.
• When red cells and plasma are separated from whole blood, small amounts of residual plasma and/or leukocyte debris may remain in the red cell concentrate.
• During blood storage, these leukocytes release cytokines, which when transfused can cause transient fevers, chills, and malaise without hemolysis.

• Management includes stopping the transfusion to exclude other serious reactions, administering antipyretics, and using leukoreduced blood products for future transfusions.
• Leukoreduction involves reducing the number of transfused leukocytes through filtering or other methods such as saline washing, freezing and deglycerolizing, or buffy coat removal.
• It also reduces the risk of human leukocyte antigen alloimmunization and transmission of cytomegalovirus (which typically resides in leukocytes).
• Premedication with antipyretics and antihistamines has not been shown to significantly reduce transfusion reactions.

• Under-anticoagulation can lead to worsening of thrombotic disease, and such patients should be started on intravenous heparin (or subcutaneous low molecular weight heparin) until a therapeutic INR is achieved with warfarin.
• Such cases should not be considered anticoagulation failures that warrant placement of an IVC filter.

• 1. Monoclonal protein in serum or urine
• 2. More than 10% clonal plasma cells in bone marrow or soft
• 3. Tissue/ bone plasmacytoma
• 4. End-organ damage (CRAB)
• 5. Calcium elevation
• 6. Renal insufficiency
• 7. Anemia (usually normocytic)
• 8. Bone pain (usually due to lytic lesions)

• Multiple myeloma is due to a malignant monoclonal proliferation of plasma cells. Patients typically develop back or bone pain, renal insufficiency, hypercalcemia, and hyperproteinemia.
• Serum and/or urine protein electrophoresis will show a monoclonal protein, and bone marrow biopsy will show >10% monoclonal plasma cells in most cases.

• Skeletal surveys should be performed at the time of MM diagnosis to assess the extent of skeletal involvement, and may sometimes identify impending pathologic fractures.
• Conventional skeletal surveys typically reveal punched-out lytic lesions, diffuse osteopenia, or fractures in nearly 80% of patients.
• Common sites for lytic lesions include vertebral bodies, skull, thoracic cage, pelvis, and proximal humerus and femur.

• Other imaging modalities (computed tomography, magnetic resonance imaging, and positron emission tomography) are usually reserved for patients with bone pain and negative initial x-ray skeletal surveys.
• Studies requiring iodinated radiocontrast agents should be avoided in myeloma patients with renal insufficiency.

Technetium-99m bone scans detect primarily blastic bony lesions. However, bone scan is much less sensitive than conventional x-ray for the lytic lesions of MM.

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• Although more common in Waldenstrom's macroglobulinemia (due to elevated lgM), hyperviscosity syndrome can also occur in patients with multiple myeloma (MM).
• The hyperviscosity in myeloma is typically due to increased serum protein content with large molecular size, abnormal polymerization, and abnormal immunoglobulin shape.
• The impaired microcirculation in the brain can cause headache, dizziness, vertigo, nystagmus, hearing loss, and visual impairment.
• Severe cases can present with somnolence, coma, seizures, and heart failure.
• Mucosal hemorrhage (eg, nasal or oral bleeding) is usually due to impaired platelet function.
• Treatment involves prompt plasmapheresis for symptom relief.

Surgery is the first line treatment for SCC. Radiation therapy is an alternative.

• It is an X·linked recessive disorder that occurs almost exclusively in males.
• Females are usually asymptomatic carriers of the disease, although mild bleeding is possible in carriers.
• A female may acquire hemophilia in the rare situation in which her father has hemophilia and her mother is a carrier who transmits the abnormal allele to her.
• Daughters born to an affected father and a normal mother will be carriers.
• Sons born to a carrier mother have a 50% chance of having hemophilia.

• Focal external beam radiation therapy is the treatment of choice for palliation of pain in patients with metastatic, advanced hormone-refractory prostate cancer.
• It should be used in patients with a single or few focal bone lesions in which the pain is not adequately controlled with narcotic analgesics.

• Chronic myeloid leukemia (CML) is caused by a translocation of chromosomes 9 and 22, which produces the Philadelphia chromosome.
• The presence of the bcr/abl fusion protein is diagnostic of CML and results in unregulated tyrosine kinase activity.
• Tyrosine kinase inhibitors such as imatinib are the initial treatment of choice in almost all instances.
• Later, BMT can be offered to patients who are young with stable disease and who have a suitable donor.

In contrast to patients with idiopathic DVTs, patients with DVTs secondary to reversible or time-limited risk factors (eg, surgery, pregnancy, oral contraceptive use, or trauma) should be treated for at least three months but not longer than six months, as the risk of a recurrent DVT after six months of treatment is very low.

• In patients with idiopathic DVTs, at least six months of warfarin therapy is also recommended, with re evaluation at the end of the treatment cycle for long-term anticoagulation.
• This decision is individualized and should be based on the risk to benefit ratio for anticoagulation.

• Pernicious anemia is characterized by the autoimmune destruction of parietal cells.
• The two major implicated auto-antibodies that have been described are the anti-parietal and anti-intrinsic factor (IF) antibodies.
• Anti IF antibody testing is the recommended initial test for the detection of pernicious anemia.