ABIM 2015 - Heme/Onc Flashcards
What does the surface marker CD34 say about that cell?
That it is a STEM cell
Aplastic Anemia, Pure Red Cell Aplasia, Neutropenia and Thrombocytopenia are all caused by what failure?
Bone Marrow Failure
PANcytopenia with hypocellular bone marrow caused by Heredity, Idiopathic, Immune Dysfunction (Drugs, Infections, Toxins or Radiation)?
Aplastic Anemia
The hematopoietic, pluripotent STEM cell gives rise to two STEM cells, the MYELOID STEM Cell and the LYMPHOID STEM Cell. What does the LYMPHOID STEM Cell give rise to?
B & T Lymphocytes ONLY
RBCs (Erythrocytes), WBCs (Granulocytes, Monocytes, Basophils, Eosinophils) and PLATELETS come from what STEM Cells?
MYELOID STEM Cells
What is another name of GRANULOCYTE (part of the WBCs and therefore the Myeloid lineage)?
NEUTROPHIL (Segments and Bands or “Stabs”)
Neutrophils (granulocytes) + Basophils + Eosinophils = ?
Polymorphonuclear cells (PMNs) - their Nuclei are MULTI-lobulated
What do FEMALE Neutrophils (granulocytes) have that MALE Neutrophils DO NOT?
X-chromosome structure
What is the NORMAL number of segments that a mature Neutrophil has?
3-5
What is an IMMATURE Neutrophil called?
A “band” or “stab” cell
What is the most ABUNDANT WBC in the blood?
The Neutrophil
What is a reticulocyte?
An immature RBC (that has a nucleus - mature RBCs do not)
What is the Absolute Neutrophil Count (ANC) of Moderate Aplastic Anemia?
500-1,000/µL
What is the Absolute Neutrophil Count (ANC) of Severe Aplastic Anemia?
200-500/µL
What is the Absolute Neutrophil Count (ANC) of VERY Severe Aplastic Anemia?
The most common CONGENITAL Aplastic Anemia with Skin defects, Short stature, HYPOgonadism, MICROcephaly and Urogenital abnormalities is called?
FANCONI Anemia
Fatigue, Exertional Dyspnea, Bleeding and Infections are seen in this anemia?
Aplastic Anemia
What MUST a CBC demonstrate to diagnose Aplastic Anemia?
Neutropenia AND Thrombocytopenia (or, PANcytopenia)
How is Aplastic Anemia diagnosed?
Bone Marrow aspirate AND Biopsy
What do patients with classic Paroxysmal Nocturnal Hemoglobinuria (PNH) develop later?
Aplastic Anemia
When is treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH) started?
When HEMOLYSIS occurs
How should patients YOUGER than 40 with an HLA-compatible sibling be treated for Severe Aplastic Anemia?
By Allogenic (same species) Hematopoietc Stem Cell Transplantation (75-90% CURE)
How should patients who are NOT candidates for Stem Cell Transplantation be treated for Severe Aplastic Anemia?
Immunosuppressants (anti-Thymocyte globulin and Cyclosporine) antithymocyte globulin is animal-derived Ab against human T-cells
Pts who survive Aplastic Anemia have a risk of developing these two diseases?
Myelodysplasia and AML
What are the prophylactic agents used in patients with Aplastic Anemia?
Antibiotic, Antiviral and Anti-fungal agents
What type of transfusions MUST be given to pts with Aplastic Anemia if they require blood transfusion?
IRRADIATED, Leukocyte DEPLETED transfusions (of RBCs and Platelets)
Below what platelet number should pts with Aplastic Anemia receive PLATELET transfusions?
HIGH-Risk or if Platelets
Bone Marrow Aspirate and Biopsy shows a HYPOcellular bone marrow with Increased FAT space and Decreased hematopoietic elements?
Aplastic Anemia
Severe NORMOCYTIC anemia with lack of reticulocytes and no eryhtroid precursors in the bone marrow without any effect on leukocyte or platelets?
Pure RED Cell Aplasia
Medications, Toxins, Thymoma, Parvovirus B19, HIV and Autoimmune disorders are all associated with this ANEMIA type?
Pure RED Cell Aplasia
What diagnostic tests should be done to confirm Pure RED Cell Aplasia?
CT (to exclude thymoma), Peripheral Blood of Bone Marrow Flow Cytometry and serologic evaluation for autoimmune disorders
What should you test a patient for who already has an underlying Hemolytic Anemia and presents with an ACUTE severe HYPOproliferative anemia (deficient erythropoietin)?
Parvovirus B19
What type of Anemias are caused by Erythropoietin deficiency?
NORMOCYTIC
A patient with Pure RED Cell Aplasia was found to have a large number of granular LYMPHOCYTES with abundant cytoplasm and azurophilic granules infiltrating the bone marrow and also found on a peripheral smear?
Large Granular Lymphocytosis (common, malignant cause of Pure RED Cell Aplasia) - CD57-positive T-cells are diagnostic
How is Pure RED Cell Aplasia treated?
Treat the underlying cause AND TRANSFUSE RBCs as well as Immunosuppressants (Cyclophosphamide or Cyclosporine or PREDNISONE or antithymocyte globulin)
How is Parvovirus B19 treated in the normal patient and in immunocompromised patient?
No treatment necessary if immunocompetent, otherwise IVIG
What medications can CAUSE Pure RED Cell Aplasia?
Exogenous Erythropoietin (Anti-EPO Ab form), phenytoin, Isoniazid, chloramphenicol
What is the danger for a patient that is NEUTROPENIC?
Neutrophils are the MAJORITY of WBC’s so BACTERIAL and FUNGAL infections
Below what Number of Absolute Neutrophils (normal is 2,500-6,000/µL) is a patient at great risk of infections?
In some Blacks, Yemenite Jews and Arabs the Absolute Neutrophil Count (ANC) is genetically low (1,000-1,500/µL) what should be done?
NOTHING AT ALL (only
SLE and meds (CHLORAMPHENICOL, TMP-SMX, Cephalosporins, Chemotherapy drugs, Naproxen, propylthiouracil, carbamazepine, phenytoin, amiodarone and procainamide) can ALL cause what type of SERIOUS ANEMIA?
NEUTROPENIA (severely decreased Absolute Neutrophil Count - with high risk for infection)
RA with Splenomegaly AND Neutropenia?
FELTY Syndrome
How is Neutropenia diagnosed?
Bone Marrow Evaluation
How is Neutropenia treated?
STOP offending drug or treat Underlying disease
Although treating patients with SEVERE Congenital Neutropenia (ANC
Myelodysplasia and AML
Is ISOLATED Thrombocytopenia associated with a Bone Marrow or Stem Cell disorder?
NO!! (these are usually acquired - meds, toxins, etc.)
Chemotherapy, radiation, inherited defects in DNA repair (FANCONI Anemia), and Down Syndrome can all have this Hematopoietic STEM Cell disorder?
Myelodysplastic Syndrome
What does Myelodysplastic Syndrome (Myelodysplasia) transform to?
AML (associated with Sweet Syndrome - neutrophillic infiltrate on biopsy)
Bone Marrow biopsy revealing HYPERcellularity and Dysplasia (abnormal cells) of Myeloid lineage (erythrocytes, neutrophils, basophils, eosinophils, platelets) is what?
Myelodysplasia
The NUMBER of affected cell lineages (neutrophils, platelets, erythrocytes, basophils, eosinophils), amount of Blasts (immature cells) and advanced age are associated with what?
Prognosis of a patient with Myelodysplasia (if >5% blasts or multilineages - poor prognosis)
When should IRON chelation therapy be started?
When serum ferritin level ≥1,000 ng/mL
How are the anemias of Myelodysplasia treated?
RBC or Platelet transfusions (can cause iron overload)
What is considered a “Dysplastic” neutrophil?
One that has a decreased amount of granules and 5 segmented lobes of the nucleus
What is a HYPOgranular Neutrophil with a bi-lobed nucleus in a patient with Myelodysplasia called?
Pelger-Huet morphology
What two chemotherapeutic agents are BEST for treating Myelodysplasia?
AZAcitidine and DECitabine (decreased progression to AML and less transfusions required)
What is the BEST treatment for the LOWER-Risk, transfusion-dependent Myelodysplasia with Chromosome 5q deletion?
LENALinomide
What GENETIC feature predicts good response to Immunosuppressive therapy in patients with Myelodysplasia?
HLA-DR15 and younger age
What is CURATIVE treatment in patients with Myelodysplasia but is reserved for YOUNGER patients with HIGH-RISK disease due to its high mortality risk?
Allogenic (same species) Hematopoietic Stem Cell Transplantation (HSCT)
A patient that presents with features of Myelodysplasia BUT has Weight LOSS, Sweats and Splenomegaly with LEUKOCYTOSIS and HIGH Monocyte count likely has?
Chronic MyeloMonocytic Leukemia (CMML)
What hematologic condition is associated with Down Syndrome that eventually transforms to AML?
Myelodysplasia
What should be done for a patient with Myelodysplasia with LOW-Risk disease who is asymptomatic?
OBSERVATION ONLY
What agents can improve Hb in patients with lower-risk Myelodysplasia with SYMPTOMATIC Anemia?
Erythropoiesis-stimulants (Epoetin and Darbepoetin)
A Myeloproliferative disorder in which ALL of the circulating erythrocytes, leukocytes and platelets (all the myeloid lineages) are derived from a SINGLE NEOPLASTIC STEM CELL and can grow and divide WITHOUT erythropoetin?
Polycythemia Vera
Hyperviscosity of blood with thrombosis in a patient 50-75 years old with bone marrow fibrosis and HEPATOSPLENOMEGALY (because hematopoietic activity is driven into the liver and spleen) with PRURITUS after BATHING, BURNING of the PALMS and SOLES (erythromelalgia) with FEVER, WEIGHT LOSS and SWEATING, GI BLEEDING, confusion, TIA-like symptoms, tinnitus, blurred vision and HA?
Polycythemia Vera
What liver disorder can Polycythemia Vera cause BESIDES Hepatomegaly?
Budd-Chiari Syndrome (hepatic venous outflow obstruction)
Elevated Hct with MICROCYTOSIS and a LOW or Undetectable Erythropoetin level with normal oxygen Saturation with elevated serum uric acid and Vit B12 levels?
Polycythemia Vera
JAK2 protein MUTATION?
Polycythemia Vera
Is Polycythemia Vera a possibility if the JAK2 protein mutation is absent and erythropoietin level is normal or high?
NO!!
What are mimics of Polycythemia Vera which are called Secondary Erythrocytosis?
Sleep Apnea, Emphysema, CO-poisoning, Smoking, Renal Artery Stenosis
What medication decreases thrombosis in Polycythemia Vera and should be given to ALL patients?
ASPIRIN
What therapy provides the BEST overall survival for Polycythemia Vera?
Phlebotomy 1-2x/week until Hct
What can be used to treat Polycythemia Vera in PREGNANCY?
Interferon-alpha
What else besides Aspirin and Phlebotomy should be added in patients >60 years old who have had previous thrombotic episodes?
Hydroxyurea
Elevated PLATELET count (≥600,000/µL) on TWO occasins 1 MONTH apart, with normal platelets due to INCREASED Megakaryocyte production with microvascular thrombi, DIGITAL Ischemia, hemorrhagic symptoms and splenomegaly?
Essential Thrombocythemia
How is Essential Thrombocythemia treated?
Anti-platelet agents
What condition can Iron deficiency, chronic bleeding, cancer, inflammation, infection or post-splenectomy mimic and must be excluded?
Essential Thrombocythemia
The ABSENCE of what chromosome excludes CML in the setting of Essential Thrombocythemia?
Philadelphia Chromosome
What disease does Polycythemia Vera (like Myelodysplasia) progress to?
AML
Does Essential Thrombocythemia progress to AML (like Polycythemia Vera and Myelodysplasia do)?
NO!!
What is the MAJOR complication of Essential Thrombocythemia?
Venous and arterial thrombosis
When in patients with Essential Thrombocythemia do you see PSEUDOhyperkalemia and PSEUDOhypoglycemia and bizzare platelet morphology?
When platelet counts ≥1-1.5 MILLION (because platelets use glucose and release potassium)
Clusters of ABNORMAL megakaryocytes in the bone marrow are found in what disease?
Essential Thrombocythemia
What is the BEST therapy for Essential Thrombocythemia?
Hydroxyurea + Aspirin
What therapy can be used in PREGNANT women who have Essential Thrombocythemia (also used for Polycythemia Vera?
Interferon-alpha
What medication can be used for the treatment of Essential Thrombocythemia and Polycythemia Vera in patients who are older and CANNOT tolerate the side effects of other drugs?
32P (radioactive isotope) - HIGH risk of leukemia
What leukemia is the Philadelphia Chromosome seen in?
CML t(9;22) BCR-ABL tyrosine kinase
What two other Leukemias does CML manifest as during the BLAST phase?
AML (80%) and ALL (20%)
SPLENOMEGALY, fatigue, night sweats, weight loss, abdominal discomfort, early satiety and bleeding with HIGH leukocyte count, HYPERcellular bone marrow with myeloid hyperplasia?
CML (chronic phase)
How is CML diagnosed?
By demonstrating either t(9;22) or BCR-ABL transcript
What patients, if diagnosed with CML, require treatment?
ALL of them, EVEN if ASYMPTOMATIC
What are the BEST three drugs that treat CML?
BCR-ABL inhibitors (imaTINIB, niloTINIB, dasaTINIB)
In patients who cannot tolerate the BCR-ABL inhibitors (-“tinib”) or are in the accelerated or bast phases of CML rather than the chronic phase, what can be done?
Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
What is the most common PHYSICAL EXAMINATION finding in patients with CML?
Splenomegaly
Abnormal MYELOID and MEGAKARYOCYTE proliferation stimulating collagen production, bone marrow fibrosis and therefore impaired bone marrow function driving hematopoiesis into the spleen and liver with resultant HEPATOSPLENOMEGALY and bone pain?
Myelofibrosis
Anemia with nucleated erythrocytes and TEAR-DROP erythrocytes, elevated LDH, Uric acid and Alk Phos (bone)?
Myelofibrosis
How is Myelofibrosis diagnosed?
Bone marrow biopsy, also has JAK2 mutation (as with Polycythemia Vera and Essential Thrombocythemia)
How is Myelofibrosis treated?
Symptomatic (transfusions, hydroxyurea - for symptomatic hepatosplenomegaly and thrombocytosis, Danazol)
This medication is used in myeloproliferative diseases, especially Polycythemia Vera and Essential Thrombocythemia as well as for symptomatic relief of the effects of hepatosplenomegaly and throbocytosis in those patients, also used in Sickle Cell anemia as it breaks down cells that sickle and increases production of fetal Hb?
Hydroxyurea
What is a CURATIVE treatment for Myelofibrosis but as usual, has a high rate of morbidity and mortality in oder patients?
Allogenic Hematopoietic Stem Cell Transplantation (HCST)
What is done for treatment of asymptomatic patients with Myelofibrosis?
Observation ONLY
What disease is caused in part by the abnormal proliferation of megakaryocytes that causes excess fibroblast growth factors stimulating collagen production and therefore marrow fibrosis driving hematopoiesis into the liver and spleen?
Myelofibrosis
What leukemia is associated with the presence of Auer Rods and circulating myeloblasts?
AML
Having had Myelodysplasia (or other bone marrow failure syndromes) or a Myeloproliferative disorder (Polycythemia Vera, Essential Thrombocythemia), Fanconi Anemia (DNA repair defect) and Down Syndrome places one at risk for this disease?
AML
Violaceous non-tender cutaneous plaques and gingival hyperplasia can be seen in a patient with what leukemia?
AML
What neutrophilic dermatologic condition can be seen in AML or in Myelodysplasia that is about to convert to AML?
Sweet Syndrome
Tumor lysis syndrome and DIC with severe cytopenias, hypercellular bone marrow showing a monotonous population of blasts (≥20%) or promyelocytes?
AML
What cytochemical stain can differentiate myeloblasts from lymphoblasts?
Myeloperoxidase
What patients have a favorable survival of AML?
YOUNGER than 55, t(8;21), t(15;17)-APL or inv(16)
How are all leukemias treated supportively?
Transfusions when needed and management of deficient cells (infections in pts with neutropenias or anti-platelet agents in pts with thrombocythemias)
What is TUMOR LYSIS SYNDROME and what conditions is it seen in?
Breakdown products of dying cells causing acute renal failure with ELEVATED (potassium, phos, uric acid) and LOW (calcium); caused by AML and the treatment of certain cancers (lymphomas, leukemias)
How is Tumor Lysis Syndrome [(caused by the breakdown products of dying cells resulting in acute renal failure with ELEVATED (potassium, phos, uric acid) and LOW (calcium)] treated?
IVF, RASBURICASE, and ALLOPURINOL
The leukocytosis that can be seen in CML and AML, especially when >50,000/µL can cause what symptoms?
CNS and Respiratory (HA, visual, AMS, hypoxia)
How is DIC managed in patients with AML?
Transfusions (if Acute PROmyelocytic Leukemia, can add ALL-trans-retinoic acid)
How are symptoms (CNS, pulmonary) of leukocytosis (>50,000/µL) in AML or CML treated?
Hydroxyurea or Leukapheresis
How is AML treated?
7-days of cytarabine and 3-days of an anthracycline -“rubicin”)
What is “Consolidation” therapy in oncology?
Chemotherapy used to eradicate minimal RESIDUAL disease such as seen in AML after the (“7 and 3”) treatment
Why is CYTARABINE (standard induction chemotherapy used in AML) not used in adults >55?
Because of cerebellar toxicity and increased mortality
What is considered CURATIVE treatment for AML?
Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
How is Acute ProMyelocytic Leukemia (APL)-a variant of AML-distinguished from Acute Myelocytic Leukemia (AML)?
By the presence of t(15;17) - more favorable outcome in patients
The addition of WHAT drug to STANDARD induction chemotherapy (7-days cytarabine + 3-days of an anthracycline -“rubicin”) can produce an 80% cure rate in patients with Acute ProMyelocytic Leukemia (APL)?
All-trans-retinoic acid (ALTRA) or arsenic trioxide (QT-prolongation)
Blood or bone marrow with ≥20% myeloblasts is a diagnosis of?
AML
Symptoms over days to weeks of fatigue, dyspnea, bleeding, infections and fever with sweats and weight loss are related to what?
Bone marrow failure
Lymphadenopathy with Hepatosplenomegaly, large anterior mediastinal mass causing Superior Vena Cava syndrome (obstruction of the SVC causing facial edema, venous distention in the neck, UE edema, HA and dyspnea), pleural effusions with circulating LYMPHOblasts and tumor lysis syndrome?
ALL (acute LYMPHOblastic Leukemia)
≥25% LYMPHOblasts on bone barrow examination is a diagnosis of what?
ALL (Acute Lymphoblastic Anemia)
Why would ALL be NEGATIVE for myeloperoxidase test?
Because it is a LYMPHOblastic disease not MYELOblastic
What are poor prognostic factors in a patient with ALL besides age >55?
A LEUKOCYTE count >30,000/µL and B-lymphocyte disease rather than T-lymphocyte disease
What happens in BOTH AML and ALL shortly after the commencement of chemotherapy?
Tumor Lysis Syndrome (treat with IVF, Allopurinol and Rasburicase)
What patients CANNOT use RASBURICASE (to treat tumor lysis syndrome) because it induces HEMOLYSIS?
Those with a glucose-6 phosphate dehydrogenase deficiency (G6PD)
What feature can ALL (RARELY) have that is usually seen in CML patients and requires addition of additional chemotherapy agent use?
Philadelphia Chromosome t(9;22) BCR-ABL (-“tinib”)
Anthracycline (-“rubicin”) + Vincristine + L-asparginase + Corticosteroid is the chemotherapeutic regimen for what leukemia?
ALL (add a -“tinib” if Philadelphia Chromosome positive)
What CURATIVE therapy can be given to patients with high-risk ALL that are otherwise healthy and younger than 55?
Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
Because of the RISK of CNS involvement in patients with ALL, how is chemotherapy given ± radiation therapy?
Intrathecally (into spinal canal)
What patients WITH CANCER should be given Erythropoiesis Stimulating Agents (epoetin or darbapoetin) and whom should these NOT be given to and why?
Only those patients WITH CANCER who suffer from CHEMOTHERAPY-related anemia (Hb ≤10) for whom the treatment is NOT curative (because it causes thromboembolism and poor tumor control)
What patients WITHOUT CANCER are Erythropoiesis Stimulating Agents (epoetin and darbapoetin) used in?
Those with anemia (Hb≤10) with KIDNEY FAILURE (whether on dialysis or not)
What is the purpose for using Erythropoiesis Stimulating Agents (epoetin and darbapoetin)?
To reduce dependence on transfusions
What is the TARGET Hb at which time Erythropoietin Stimulating Agents (epoetin and darbapoetin) should be discontinued and why?
Hg ≥11 g/dL (because of higher rate of all-cause mortality, cardiovascular events and stroke
What prophylactic medication is given to patients whom are undergoing myelosuppressive chemotherapy to reduce associated risk of febrile-NEUTROPENIA?
G-CSF (GRANULOCYTE-Colony Stimulating Factors) “granulocyte” is synonymous with “neutrophil”
Immunosuppressive therapy (in Allogenic method to prevent GVHD - graft vs host disease) in conjunction with administration of Myeloablative doses of cytotoxic chemotherapy with total body irradiation followed by stem cell infusion?
Hematopoietic Stem Cell Transplantation (HSCT); allogenic (HLA-matched donor) is better tolerated than autologous (own cells used after massive doses of G-CSF are given)
In what kind of Hematopoietic Stem Cell Transplantation (HSCT) technique is the risk of Opportunistic Bacterial, Viral and Fungal infections (Pneumocystis jirovecii pneumonia, Aspergillosis, HSV, CMV) highest?
ALLOGENIC HSCT (rather than autologous), because in order to prevent Graft Vs Host Disease, Immunosuppression MUST be used
What cells do B-lymphocytes differentiate into that secrete a large number of ANTIBODIES (immunoglobulins)?
PLASMA cells (differentiated B-lymphocytes that secrete a large number of antibodies “immunoglobulins”)
MGUS, Amyloidosis, Multiple Myeloma and Waldenstom macroglobulinemia are all MALIGNANCIES caused the Abnormal Proliferation of these types of cells?
PLASMA cells (differentiated B-lymphocytes that secrete a large number of antibodies “immunoglobulins”)
Blacks, ≥70 yo, with a malignancy of PLASMA cells producing a Monoclonal (M) protein consisting of either IgG, IgA or IgD (heavy chains) and a K (kappa) or a Lambda light chain?
Multiple Myeloma
Black, ≥70 yo with bone pain from lytic bone lesions, spinal cord compression with neurologic symptoms (bowel or bladder dysfunction) and sinus/pulmonary infections?
Multiple Myeloma
What should be done for a patient with or without Multiple Myeloma that presents with bowel or bladder dysfunction attributed to spinal cord compression?
EMERGENCY!!
ANEMIA with rouleaux formation, leukopenia, HYPERCALCEMIA and elevated CREATININE?
Multiple Myeloma
Where are filtered monoclonal light-chains causing CAST Nephropathy found?
Multiple Myeloma
How is Multiple Myeloma diagnosed?
Protein Electrophoresis, Immunofixation of Serum, 24-hour urine collection with identification of the M-protein (one heavy chain IgG, IgA or IgD with one light chain - kappa or lambda)
Which are the ONLY two radiologic studies that can be used to detect Multiple Myeloma (lytic bone lesions)?
Myeloma BONE SURVEY (plain radiographs of the skeleton) or MRI
What causes spinal cord compression with bowel and bladder dysfunction in patients with Multiple Myeloma and is an EMERGENCY?
Bone fragments from vertebral body compression fractures caused by lytic bone lesions or plasmacytomas
What must be present on Bone Marrow biopsy for Multiple Myeloma to be diagnosed as “SYMPTOMATIC”?
≥10% clonal PLASMA cells, the PRESENCE of ANY amount of the M-protein and evidence of end-organ damage (lytic bone lesions)
What type of Multiple Myeloma does a patient have who presents with ≥10% PLASMA cells on Bone Marrow biopsy, presence of ≥3g/dL of the M-protein but NO evidence of end-organ damage (lytic bone lesions)?
ASYMPTOMATIC (smoldering) Multiple Myeloma
What can be used to predict the time to progression of ASYMPTOMATIC (smoldering) Multiple Myeloma to SYMPTOMATIC Multiple Myeloma?
Amount of PLAMSA cells and M-protein level
What does a patient have if presents with NO SYMPTOMS but was found on Bone Marrow biopsy to have the M-protein although
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Which is the ONLY type of Multiple Myeloma that REQUIRES treatment?
SYMPTOMATIC Multiple Myeloma
What does it mean in Monoclonal Gammopathy of Undetermined Significance (MGUS) when the M-protein found is ≥1.5 g/dL OR that the M-protein is not IgG but rather IgA or IgD?
Higher RISK of PROGRESSION (to Multiple Myeloma, Amyloidosis and Waldenstrom macroglobulinemia)
What are the CORE meds that are used to treat Multiple Myeloma?
Thalidomide, Lenalidomide, Bortezomib and Melphalan
Can Thalidomide and Lenalidomide be used in pregnant women?
NO WAY (teratogenic and thrombogenic)
Thalidomide and Bortezomib, drugs used to treat Multiple Myeloma, have this significant side effect?
Peripheral Neuropathy
Lenalidomide and Melphalan, drugs used to treat Multiple Myeloma, have this significant side effect?
Myelosuppression
What should ALWAYS be considered PRIOR to starting chemotherapy agents for treatment of Multiple Myeloma?
Candidacy for AUTOLOGOUS Hematopoietic Stem Cell Transplantation (HSCT)
What bisphosphonates are used in Multiple Myeloma with lytic bone lesions?
Pamidronate or Zoledronic acid
Focal Segmental Glomerulosclerosis (FSGS), Acute Tubular Necrosis (ATN), osteonecrosis of the jaw with poor dentition or after dental procedure can occur with these meds, used in Multiple Myeloma for lytic bone lesions?
Pamidronate and Zoledronic acid (Bisphosphonates)
How is Multiple Myeloma-related kidney injury treated?
By treating HYPRcalcemia and bisphosphonates as well as PLASMAPHERESIS (to reduce light-chains and real casts)
How often should patients with ASYMPTOMATIC Multiple Myeloma be monitored for progression?
Every 3-6 months
Prior to starting bisphosphonate therapy in a patient, what MUST be done in order to avoid bisphosphonate associated osteonecrosis of the jaw?
Dental evaluation
What agents MUST be avoided in patients with Multiple Myeloma so as to prevent further kidney injury already caused by light-chain casts (which is an indication in itself to start aggressive Multiple Myeloma chemotherapy)?
NSAIDS, CT contrast agents, gadolinium, loop diuretics
Incidentally found on SPEP (Serum Protein Electrophoresis), an M-protein (a heavy chain: IgG, IgA or IgD plus a light chain Kappa or Lambda)
Monoclonal Gammopathy of Undetermined Significance (MGUS)
If a patient presents with symptoms suggestive of Multiple Myeloma, what should be tested first?
24-hour urine protein electrophoresis to look for the M-protein
If a PLASMA cell disease is suspected in a symptomatic patient after finding the M-protein in the serum or urine, what should be the next diagnostic step?
Bone marrow biopsy to establish the need for treatment
What is the risk of progression of MGUS to a clinically significant PLASMA cell disorder?
VERY low, about 1% per year
Do most patients with MGUS progress to Multiple Myeloma?
NO!!
Are most cases of Multiple Myeloma preceded by MGUS?
YES
What can IgG, IgA (heavy chains) or a purely light chain (Kappa or Lambda) MGUS progress to?
ANY PLASMA cell disease (Multiple Myeloma, Amyloidosis)
What can IgM MGUS progress to?
ONLY a B-cell non-Hodgkin lymphoma like Waldenstrom macroglobulinemia or amyloidosis
How often should patients with MGUS be monitored for?
Every 6-12 months as well as Bone Mineral Density testing at baseline (because MGUS is associated with osteoporosis)
Deposition of protein fibrils in tissues with subsequent end-organ damage is seen in what disease?
Amyloidosis
Which protein fibrils are deposited in tissues with amyloidosis?
Lambda (most common) and Kappa LIGHT CHAINS
Nephrotic proteinuria with worsening kidney function, Restrictive cardiomyopathy (when heart is involved) and hepatomegaly (when liver is involved), symmetric distal sensorimotor neuropathy, carpal tunnel syndrome, autonomic neuropathy and orthostatic hypotension can ALL be seen with this disease?
Amyloidosis
Periorbital purpura and macroglossia are two characteristic findings seen in this disease?
Amyloidosis
Finding of AMORPHOUS EOSINOPHILIC material from an abdominal FAT PAD aspirate or Bone Marrow biopsy with APPLE GREEN BIREFRINGENCE when stained with CONGO RED dye is characteristic of?
Amyloidosis (clonal light chains)
If Amyloidosis is diagnosed, what should be checked next?
The HEART (ECG, ECHO (TTE) - interventricular septal hypertrophy, restrictive heart disease, “sparkling” myocardium)
What is the treatment for Amyloidosis?
Dexamethasone + Melphalan
What is a CURATIVE treatment for Amyloidosis used for young patients (
Autologous Hematopoietic Stem Cell Transplantation (HSCT)
A B-cell LYMPHOMA consisting mainly of LYMPHOCYTES and PLASMA cells characterized by the production of monoclonal IgM antibodies found usually in elderly WHITE men?
Waldenstom macroglobulinemia
Lymphadenopathy, Hepatosplenomegaly (as found in ALL), Hyperviscosity (as found in proliferative disorders like polycythemia vera), CNS symptoms, Retinal Hemorrhages,, peripheral sensorimotor neuropathy (as seen with Amyloidosis), mucosal bleeding (nasal) from platelet dysfunction and Anemia with rouleaux formation are all seen in?
Waldenstrom macroglobulinemia
Bone Marrow biopsy demonstrating >10% of a lymphoplasmacytic lymphoma with IgM M-protein?
Waldenstrom macroglobulinemia
Should ASYMPTOMATIC patients with Waldenstrom macroglobulinemia be treated?
NO!! (just as you would not treat an ASYMPTOMATIC patient with Multiple Myeloma)
What should be done with a patient that manifests with HYPERviscosity syndrome with Waldenstrom macroglobulinemia?
EMERGENT Plasmapheresis!!
How is Waldenstrom macroglobulinemia treated?
RITUXIMAB + (either an alkylating agent like chlorambucil or cyclophosphamide or nucleoside like fludarabine)
Lymphadenopathy + Hepatosplenomegaly + Hyperviscosity=?
Waldenstrom macroglobulinemia
What is the measure of the blood volume that is composed of erythrocytes (RBCs)?
Hematocrit (Hct)
What portion of the CBC tells you about the SIZE of the erythrocytes (RBCs)?
MCV (Mean Corpuscular Volume)
Why is the normal Hb level in men higher than that of women?
The eryhtropoietic effect of Androgens
What is normal erythrocyte production controlled by?
Erythropoietin which is MADE by the KIDNEYS in response to HYPOXIA
CBC with Microcytosis and Anisocytosis (RBCs of unequal size) with Poikilocytosis (RBCs of abnormal shape) are found in?
IRON-deficiency anemia
CBC with Macrocytosis is found in?
Vitamin B12 (Cobalamin), Folate deficiency or Myelodysplasia
Removal of what organ and disease of what other organ can cause target RBCs?
Splenectomy; Liver disease
TTP, HUS, DIC has what type of RBC morphology?
Schistocytes (fragmented RBCs)
Hemolysis, Hypoxia, Bone Marrow Stress has what type of RBC morphology?
Nucleated RBCs (reticulocytes)
Teardrop RBCs are found in?
Myelofibrosis
Bite Cells (RBCs) are found in what condition?
G6PD deficiency
Burr Cells “echinocytes” (RBCs) are found in what condition?
Kidney disease
Spur Cells “acanthocytes” (RBCs) are found in what condition?
SEVERE Liver Disease (can also see target cells as in splenectomy and Thalassemia)
Spherocytes (RBCs) are found in what condition BESIDES hereditary spherocytosis?
WARM (antibodies) autoimmune Hemolytic Anemia
Target Cells (RBCs) are typically found in what disease (aside from splenectomy and Liver disease?
Thalassemia
Drug toxicities, Myelodysplasia and Alcohol can cause formation of what types of RBCs?
Macrocytic (as seen in cobalamin and folate deficiency)
Why do pregnant, lactating women and normal child growth present with mild MICROcytic anemias?
Because those states have INCREASED iron utilization
In MEN and NON-menstruating WOMEN, the most common reason for IRON Deficiency is?
GI blood loss
Where is IRON absorbed in the intestine?
The SMALL bowel
PICA (eating ice, clay, starch, paper) is caused by what?
IRON deficiency
What nail findings are seen in a patient with SEVERE iron deficiency?
Spooning (koilonychia)
Reduced serum IRON, Reduced serum FERRITIN, Reduced TRANSFERRIN saturation (Iron/TIBC), Increased TIBC indicate?
Iron deficiency
Which IRON measure is an ACUTE Phase Reactant which even in the setting of IRON deficiency, can be NORMAL or ELEVATED if Inflammation is present?
FERRITIN
Regardless of FERRITIN being an acute phase reactant, ABOVE what value and BELOW what value is IRON deficiency an ABSOLUTE or IMPOSSIBLE regardless of the presence of inflammation?
Ferritin >100, NO possibility of Iron deficiency
Ferritin
What blood component is ELEVATED in IRON deficiency?
Platelets (thrombocytosis) due to blood loss
What is the best IRON supplement to use for IRON deficiency?
Ferrous Sulfate, 325 mg po TID (66 mg iron per dose)
Why should IRON supplements not be taken with meals, antacids, antibiotics?
Hinders proper absorption
What is the BEST, most PRECISE measure of IRON deficiency?
Low HEPCIDIN levels (iron regulatory peptide made by the liver)
In the acidic environment of the stomach, COBALAMIN (vitamin B12) is bound to R-binders found in the SALIVA and GASTRIC SECRETIONS. In the ALKALINE Small Bowel, the COBALAMIN is transferred from the R-binders to INTRINSIC FACTOR (IF) which is NECESSARY for absorption of the COBALAMIN in the ILEUM after which it is bound to TRANSCOBALAMIN and stored in the reticuloendothelial system in the LIVER
Normal Vitamin B12 absorption and processing
What is the most COMMON cause of Cobalamin (vitamin B12) deficiency?
MALABSORPTION
Ab-directed (autoimmune) destruction of gastric parietal cells (synthesize Intrinsic Factor -IF)?
Pernicious Anemia
Pancreatic Insufficiency, Bacterial Overgrowth and Achlorhydria (low acid states) all cause COBALAMIN deficiency how?
By Malabsorption
Loss of position or vibration sense with spastic ataxia, yellow skin from hemolysis, hallucination, dementia and psychosis can all be seen in this deficiency?
COBALAMIN (vitamin B12) deficiency
Oval Macrocytes and HYPERsegmented neutrophils (>5 nuclear lobes) with thrombocytopenia and leukopenia are found in what deficiency?
COBALAMIN (vitamin B12) deficiency
FOLATE deficiency is confirmed by elevation of WHAT analyte?
HOMOCYSTEINE ONLY
COBALAMIN (vitamin B12) deficiency is confirmed by the elevation of what TWO analytes?
METHYLMALONIC ACID AND HOMOCYSTEINE
Decreased HAPTOGLOBIN, ELEVATED serum LACTATE DEHYDROGENASE (LDH) and UNCONJUGATED Bilirubin levels and a LOW RETICULOCYTE suggest what?
Hemolysis (such as with COBALAMIN deficiency)
Hemolysis with a LOW reticulocyte count suggests what?
RBC SYNTHESIS dysfunction (Bone marrow problems like myelofibrosis or decreased Iron, Cobalamin or Folate)
Why is it SO important when a patient presents with Macrocytic Anemia, that the etiology of whether it is Cobalamin or Folate deficiency is DETERMINED?
Because the anemia WILL RESPOND to supplementation of FOLATE whether folate OR cobalamin was deficient, HOWEVER it may have been caused by COBALAMIN deficiency in which case the NEUROLOPSYCHIATRIC symptoms will WORSEN and become IRREVERSIBLE
Is Methylmalonic acid increased in FOLATE deficiency?
NO!! only HOMOCYSTEINE is
What is the BEST treatment of COBALAMIN deficiency?
ORAL supplementation
Diseases with increased cell turnover such as PSORIASIS and HEMOLYTIC ANEMIAS (sickle cell anemia) as well as MALNUTRITION and ALCOHOL abuse can cause what important dietary deficiency?
FOLATE (very limited stores in body)
Can the serum folate be normal in folate deficiency?
YES!! which is why you MUST measure the HOMOCYSTEINE level if you suspect a FOLATE deficiency
What is “inflammatory anemia”?
What was called “anemia of chronic disease” in the past
Why do states of inflammation cause anemia?
Inflammatory cytokines inhibit erythropoietin production, the response to erythropoietin as well as INCREASED production of the hepatic peptide HEPCIDIN which causes DECREASED IRON absoprtion and DECREASED release of iron from erythrocytes and macrophages
Anemia with a Hb >8 g/dL, DECREASED reticulocyte levels (synthetic problem), normal to LOW (if chronic) serum IRON, LOW TIBC (no need to bind any new iron) and a HIGH FERRITIN level (
Inflammatory Anemia (formerly known as anemia of chronic disease)
States of Inflammation as well as CHRONIC heart disease and DM cause this type of anemia?
Inflammatory Anemia (formerly known as anemia of chronic disease)
Does Inflammatory Anemia need treatment OR IRON supplementation?
NO!!! treat the UNDERLYING disease
Normochromic, Normocytic anemia with a REDUCED reticulocyte count (synthetic problem) with BURR Cells (echinocytes) in the ABSENCE of a Myelofibrotic disease?
Anemia caused by KIDNEY disease
In the setting of KIDNEY disease, if a MICROCYTIC Anemia develops, what would be the cause and how would you check for it knowing that anemia of kidney disease is NORMOCYTIC?
GI blood loss; Check Erythropoietin levels
What is the treatment of Anemia of Kidney disease?
Erythropoiesis Stimulating Agents - epoetin or darbapoetin (ONLY up to a Hb of 11!!) and INCREASE ONLY by 1 g/week otherwise risk thrombocytosis, HTN, STROKE and MI
In patients with Anemia of Kidney disease who are also on DIALYSIS, what ELSE must they be treated with BESIDES Erythropoiesis Stimulating Agents - epoetin and darbapoetin?
IRON (IV)
What should the Serum FERRITIN and IRON SATURATION be in ALL patients receiving Erythropoiesis Stimulating Agents - epoetin and darbapoetin?
Ferritin ≥100 µg/L and Iron Saturation ≥20%
Hereditary Spherocytosis, ITP, TTP, G6PD deficiency, Thalassemia, Hemoglobinopathies, Warm Autoimmune/Cold Agglutinin, Paroxysmal Nocturnal Hemoglobinuria, Microangiopathic and Drug-Induced Anemias are what type of Anemias?
HEMOLYTIC anemias
Jaundice (unconjugated - INDIRECT - bilirubinemia), pigmented gallstones, splenomegaly, elevated LDH, Haptoglobin and presence of Hemoglobinuria are common findings in this type of anemias?
HEMOLYTIC anemias
With NORMAL Bone Marrow function and Erythropoietin production, what is the TYPICAL response to HEMOLYSIS?
Increased RETICULOCYTE level (bone marrow stress)
If the etiology of a hemolytic anemia is not readily apparent, what should be the FIRST diagnostic test done to evaluate for an IMMUNE-MEDIATED hemolysis?
Coombs TEST (direct antiglobulin test)
In what HEMOLYTIC Anemia is the Bone Marrow’s ability to compensate also impaired leading to APLASTIC CRISIS?
Parvovirus B19
Whatever the ETIOLOGY of HEMOLYTIC Anemia, BESIDES treating the UNDERLYING disease, what MUST be given to ALL patients with CHRONIC hemolytic anemia?
FOLIC ACID (1 mg/day)
Mutations in the ANKYRIN protein leading SPECTRIN deficiency with loss of erythrocyte surface area leading to destabilized erythrocytes?
Hereditary Spherocytosis
Severe neonatal jaundice and severe Parvovirus B19 infection-related apalstic-crisis is seen with this hematologic defect?
Hereditary Spherocytosis
Pt has a family history of anemia, jaundice, splenomegaly and gallstones which would suggest what type of hereditary condition?
Hereditary Hemolytic anemia (hereditary Spherocytosis)
Coombs test NEGATIVE (no anti-Ab’s), OSMOTIC FRAGILITY TEST (in hypotonic saline) with 24-HOUR incubation is POSITIVE in a hemolytic anemia?
Hereditary Spherocytosis (a CONGENITAL not “autoimmune” hemolytic anemia)
In a neonate born with jaundice, to test for Ab-MEDIATED HEMOLYSIS, to see if indeed FOREIGN antibodies already adherent to the newborn’s RBCs, the NEWBORN’s blood sample is incubated after adding anti-Human globulin (anti IgG and anti-complement). The anti-Human globulin BINDS to the NEWBORN’s FOREIGN Ab’s (IF THEY ARE THERE) that may have adhered to their RBCs causing them to clump up together in a process called “agglutination”
POSITIVE DIRECT Coombs Test (Direct anti-globulin test) can also be used for TRANSFUSION reactions and Drug-induced hemolysis
To detect the presence of an RBC Ab in a patient, this test takes a sample of blood from the patient and only keeps the plasma which will have Ab’s in it. The plasma is then incubated while adding SPECIFIC RBCs with already-present antigens on them which causes the Pt’s Ab’s to BIND to the added RBCs. Adding anti-Human globulin (anti IgG and anti-complement) causes them to clump up together in a process called “agglutination”
POSITIVE INDIRECT Coombs Test (Indirect anti-globulin test)
Direct Coombs TEST result in Hereditary Spherocytosis?
NEGATIVE (a CONGENITAL not “autoimmune” hemolytic anemia)
What is the DIRECT Coombs TEST used for?
To detect an AUTOIMMUNE Hemolytic Anemia
What is the INDIRECT Coombs TEST used for?
To detect a potential MATERNAL blood incompatibility (Rh) with her fetus OR prior to giving a blood TRANSFUSION
Patients with MODERATE symptomatic anemia (those who need treatment) with Hereditary Spherocytosis should be given what treatment?
Splenectomy (with vaccination for P. pneumoniae, H. influenza and Meningococcus)
When pts are asplenic (functional or surgical), vaccinations against what must be given?
P. pneumoniae, H. influenza and Meningococcus
An X-linked erythrocyte enzyme defect most commonly found in BLACK MEN that has been found, when heterozygous, to protect against Plasmodium falciparum malaria?
G6PD deficiency
This erythrocyte enzyme deficiency results in the erythrocyte not being able to make NADPH leading to episodic hemolysis in response to oxidant stressors (infection, drugs - dapsone, TMP-SMX, nitrofurantoin and FAVA beens)?
G6PD deficiency
What is seen on a peripheral smear of a patient’s blood with G6PD deficiency?
BITE cells and Heinz bodies (denatured, oxidized Hb)
Checking G6PD levels at the same time as a hemolytic event occurred would result as NORMAL because ELEVATED G6PD would be found in young reticulocytes who have not yet matured. When would be an optimal time AFTER an acute event to check G6PD levels?
SEVERAL MONTHS after
How is a G6PD acute hemolytic crisis treated?
Supportive with discontinuation of the agent that caused the hemolysis or treatment of the infection that did
Microcytic, hypochromic erythrocytes and TARGET CELLS with IRON overload in the ABSENCE of transfusions are seen on peripheral blood smear in?
BOTH alpha and beta Thalassemia
African Americans and Middle Eastern people tend to have which Thalassemia more commonly?
alpha-Thalassemia
Mediterraneans, Indians, Asians and Pakistanis tend to have which Thalassemia more commonly?
beta-Thalassemia
How many gene deletions occur in the alpha-Thalassemia SILENT CARRIER (normal medically and hematologically)?
ONE deletion of 4 (-a/aa)
How many gene deletions occur in the alpha-Thalassemia TRAIT (or “MINOR”) (mild anemia, microcytosis, hypochromia and target cells with NORMAL Hb electrophoresis)?
TWO deletions of 4 (-a/-a) or (–/aa)
How can you distinguish IRON deficiency anemia from alpha-Thalassemia Minor (trait)?
By testing for RDW (RBC Distribution Width) which is ELEVATED in IRON deficiency but NORMAL in Thalassemia
What is the RBC Distribution Width (RDW)?
The variation in volume (size) between different RBCs in the same sample
Thalassemia associated with CHROMOSOME 16?
alpha-Thalassemia
Thalassemia associated with CHROMOSOME 11?
beta-Thaassemia
Do alpha-Thalassemia SILENT CARRIER or alpha-Thalassemia TRAIT (MINOR) require treatment?
NO
What is Hb-H disease?
alpha-Thalassemia with THREE gene deletions (–/-a)
Which alpha-Thalassemia is associated with Splenomegaly, SEVERE anemia, HF and hypoxia as well as being readily identified on Hb electrophoresis?
Hemoglobin-H (Hb-H) Thalassemia
What is Hb-BARTS?
Homozygous inheritance of a DOUBLE gene deletion where ALL four genes are deleted in alpha-Thalassemia (–/–) causing Hydrops Fetalis (death in utero)
How is Hb-H (alpha-Thalassemia with THREE gene deletions) treated?
Intermittent TRANSFUSIONS
How is beta-Thalassemia different than alpha-Thalassemia?
There are no gene “DELETIONS” just over or under EXPRESSION of the beta-globin gene
Mildly-DECREASED expression of a SINGLE (of two) beta-globin gene on Hb results in what?
beta-Thalassemia TRAIT (mild anemia, microcytosis, hypochromia and target cells) - no treatment needed
What is the Mentzer Index?
MCV/RBC count >13 is associated with beta-Thalassemia
How can beta-Thalassemia TRAIT be diagnosed in the laboratory?
Hb electrophoresis (shows increased Hb A2 and Hb F)
What is beta-Thalassemia MAJOR?
(Cooley anemia) beta-Thalassemia with almost completely ABSENT synthesis of the beta-globin chain
beta-Thalassemia associated with SEVERE anemia, growth retardation, skeletal complications and iron overload?
beta-Thalassemia MAJOR (Cooley anemia)
How is a patient with beta-Thalassemia MAJOR (Cooley anemia) treated?
Life-long blood transfusions WITH iron-CHELATION therapy and SPLENECTOMY to reduce transfusions followed by appropriate vaccination (P. pneumoniae, H. influenza, Meningococcus)
What treatment for beta-Thalassemia MAJOR (Cooley anemia) is potentially CURATIVE?
Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
What is beta-Thalassemia Intermedia?
Decreased but not absent expression of the beta-globin gene leading to a phenotype somewhere in BETWEEN beta-Thalassemia TRAIT and beta-Thalassemia MAJOR
Do you treat beta-Thalassemia TRAIT?
NO
Do you treat beta-Thalassemia Intermedia?
YES, intermittent transfusions and iron chelation therapy
9% of BLACKS have Hb-AS, what is that?
Sickle Cell TRAIT (heterozygous for Hb-S)
What is Hb-A (a2b2)?
Normal adult hemoglobin
Although considered a benign condition, this Sickle Cell Hb expression has been associated with hematuria, renal medullary carcinoma, risk of splenic rupture at high-altitudes, venous thromboembolism and sudden death during extreme conditions?
Hb(AS) or “Sickle Cell TRAIT”
What is screening recommended for all student athletes prior to participation in athletic activities?
Screening for Sickle Cell TRAIT (Hb-AS) and if positive recommend Optimal HYDRATION during strenuous activity
What is Sickle Cell DISEASE?
Patients with Sickle Cell GENOTYPES associated with HEMOLYSIS and Vasoocclusive crisis (homozygous Sickle Cell Anemia - Hb(SS), Sickle-beta Thalassemia - Hb(Sß*) and Hb(Sߺ) and Hemoglobin SC Disease - Hb(SC)
Hb(SS) - homozygous Sickle Cell Anemia and Sickle-beta Thalassemia Hb(Sߺ) have what type of presentation?
Reduced life expectancy, moderate to severe anemia and frequent pain crises
Hb(SC) and Hb(Sß*) have what type of presentation?
Less severe anemia and Less frequent vasoocclusive crises however still with ocular complications and bony infarcts
What is the BEST treatment for a patient with Sickle Cell DISEASE [Hb(SS), Hb(Sߺ), Hb(Sß*), Hb(SC)] which has shown to DECREASE mortality and is used in patients with recurrent painful episodes, acute chest syndrome and symptomatic anemia?
Hydroxyurea (increases formation of Hb-F and breaks down cells that are about to sickle)
Can a patient with Sickle Cell Disease use Hydroxyurea if they are planning to become pregnant?
NO!!
How is an UNCOMPLICATED painful Sickle Cell episode treated?
HYDRATION, ANALGESIA, Incentive Spirometry (to AVOID Acute Chest Syndrome) - discharge on hydroxyurea to decrease painful episodes and hospitalizations
What are the analgesic agents of CHOICE when treating Sickle Cell pain?
MORPHINE and Hydromorphone
Stroke, Acute Chest Syndrome, Pulmonary HTN, Priapism, Infection (from functional asplenia), Anemia are all manifestations of what?
Sickle Cell DISEASE [Hb(SS), Hb(Sߺ), Hb(Sß*), Hb(SC)]
How is a Sickle Cell Disease patient treated for STROKE?
Erythrocyte EXCHANGE Transfusion (reduce Hb-S
A patient with Sickle Cell DISEASE p/w ACUTE hypoxia, NEW infiltrate on an ENTIRE segment on CXR caused either by an INFECTION, Bone Marrow FAT embolus or a Pulmonary Infarction?
Acute Chest Syndrome
How is Acute Chest Syndrome treated?
Broad Spectrum ANTIBIOTICS, OXYGEN, PAIN Meds, Incentive SPIROMETRY to reduce atelectasis, Transfusion if needed and avoidance of overhydration
What is done EMERGENTLY for a patient with Sickle Cell DISEASE who presents either with a STROKE or Acute Chest Syndrome WITH SEVERE/PROGRESSIVE Hypoxia?
Erythrocyte EXCHANGE Transfusion
What medication given to patients with Sickle Cell DISEASE has been shown to decrease the frequency of ACUTE CHEST SYNDROME?
Hydroxyurea
A complication of Sickle Cell DISEASE that requires EMERGENT Urological Consultation for decompression if >2 hours with IVF, Pain management and Oxygenation?
Priapism
What infections are Sickle Cell DISEASE patients at higher risk for and require vaccinations?
H. influenza, P. pneumoniae, Meningococcus, Hep B and Influenza virus (yearly)
What are the three possibilities of a SEVERE ACUTE ANEMIA in a patient with Sickle Cell DISEASE?
Parvovirus B19 infection, Splenic/Hepatic sequestration or superimposed G6PD deficiency
What are the ONLY indications for Erythrocyte Transfusion in patients with Sickle Cell DISEASE?
Symptomatic Anemia (Hb-SS, Hb-Sߺ), Stroke, Acute Chest Syndrome and Surgical Intervention
Transfusion with Leukoreduced HbS-NEGATIVE, phenotypically matched for E, C and Kell antigens and alloantibodies Erythrocytes are typically used for what patients?
Those with Sickle Cell DISEASE who REQUIRE transfusion
Which are the two most commonly implicated antibodies in Autoimmune Hemolytic Anemia (AIHA)?
IgG (80%) and IgM (20%)
Abnormal IgG antibodies binding to Erythrocyte Rh antigens at 37ºC causing the cells to be Hemolysed by the SPLEEN after alteration into SPHEROCYTES by splenic macrophages with resultant MILD SPLENOMEGALY, anemia, jaundice and obviously a POSITIVE DIRECT Coombs Test?
WARM Autoimmune Hemolytic Anemia (37ºC) - POSITIVE Coombs for IgG and negative or weakly positive for C3 (complement)
How do you treat WARM Autoimmune Hemolytic Anemia?
CORTICOSTEROIDS (prednisone) and if not responsive, RITUXIMAB or SPLENECTOMY
Coombs test is positive for IgG in what type of Autoimmune Hemolytic Anemia?
WARM
Coombs test is positive for ONLY complement C3 in what type of Autoimmune Hemolytic Anemia?
COLD
Anemia worsened at cold temperatures (
Cold Agglutinin Disease (Cold Autoimmune Hemolytic Anemia)
Cold Agglutinin Disease (Cold Autoimmune Hemolytic Anemia) has been seen after INFECTIONS with what agents and results in a NEGATIVE Coombs Test for IgG, but a POSITIVE Coombs Test for complement (C3)?
Mycoplasma and EBV
What is the first line RECOMMENDATION for patients with Cold Agglutinin Disease (Cold Autoimmune Hemolytic Anemia)?
Avoidance of Cold Weather and wearing warm clothing
What is the medical treatment for Cold Agglutinin Disease (Cold Autoimmune Hemolytic Anemia)?
RITUXIMAB or Chlorambucil or Cycophosphamide (corticosteroids and splenectomy are ineffective)
For which of the Autoimmune Hemolytic Anemias are CORTICOSTEROIDS and SPLENECTOMY recommended?
WARM Autoimmune Hemolytic Anemia
What should be avoided in ALL patients with Autoimmune Hemolytic Anemias unless ABSOLUTELY necessary?
Blood Transfusions (due to acute or delayed hemolytic transfusion reactions)
Autoimmune Hemolytic Anemias that are caused by medications, typically occur DAYS to WEEKS after taking the medication and are most commonly associated with what medications?
Cephalosporins (2nd and 3rd gen)
What does the Direct Coombs Test show in DRUG-Induced Autoimmune Hemolytic Anemia?
Can be positive for IgG, C3, both or negative
How is DRUG-Induced Autoimmune Hemolytic Anemia treated?
By DISCONTINUATION of the DRUG (can be prolonged if FLUDARABINE was the drug)
What is the function of HAPTOGLOBIN and why is it DECREASED in HEMOLYTIC anemias?
Haptoglobin is found in the plasma and it BINDS free Hb that has been released by lysed RBCs (saves the Hb) therefore in the setting of a hemolytic anemia, its numbers will decrease as it binds as much of the free Hb in the plasma as it can
Why is LDH significant in hemolytic anemia?
Because it is found in LARGE amounts in RBCs and when these are lysed, it is released therefore raising its numbers significantly
Schistocytes and “helmet cells” with LOW HAPTOGLOBIN and HIGH LDH are found in what conditions?
Microangiopathic Hemolytic Anemias
Turbulent flow around mechanical heart valves, balloon pumps, ventricular assist devices and aneurysms, TTP, HUS and DIC with schistocytes and helmet cells are all seen in this type of Anemia?
Microangiopathic Hemolytic Anemia
In ANY patient with schistocytes in the blood, what should ALWAYS be checked for?
TTP (Thrombotic Thrombocytopenic Purpura),HUS and DIC (only if there is an associated coagulopathy - low platelets)
How are TTP and HUS treated?
PLASMA EXCHANGE
How is DIC treated?
Prompt treatment of UNDERLYING infection or OBSTETRIC emergencies and OFFENDING DRUG Discontinuation
FEVER + NEUROLOGIC SYMPTOMS + HEMOLYSIS =?
TTP - plasma exchange
E.coli + DIARRHEA + HEMOLYSIS =?
HUS - plasma exchange
Pt presents with hemolytic anemia, PANcytopenia, unprovoked thrombosis, mutation in PIG-A gene resulting in a decrease or ABSENCE of an important erythrocyte anchoring protein where hemolysis occurs by absence of CD55 and CD59 regulating factors?
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Detection of CD55 and CD59 deficiency on FLOW CYTOMETRY on the surface of erythrocytes and leukocytes is diagnostic for?
Paroxysmal Nocturnal Hemoglobinuria
Pancytopenia, atypical-site thrombosis such as in the mesenteric or cerebral circulation with hemolysis?
Paroxysmal Nocturnal Hemoglobinuria (PNH)
How is Paroxysmal Nocturnal Hemoglobinuria treated?
AGGRESSIVE ANTICOAGULATION and ECULIZUMAB (monoclonal Ab against the C5 terminal complement component)
What is of UTMOST importance when treating a patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) with ECULIZUMAB?
Vaccination against Meningococcus due to HIGH risk of Neisserial infection with this drug
In patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who do not respond to ECULIZUMAB, have unresponsive hemolysis and severe marrow failure, what can be done?
Immunosuppressive therapy or Allogenic Bone Marrow Transplantation
AGGRESSIVE Anticoagulation and Eculizumab are the treatment for what disease?
Paroxysmal Nocturnal Hemoglobinuria (PNH)
What is the most common cause of INFECTIOUS Hemolytic anemia caused by INTRAVASCULAR hemolysis and by the splenic removal of infected erythrocytes?
Malaria
In patients with FUNCTIONAL ASPLENIA or previous surgical splenectomy, this TICK-borne infectious agent found in CAPE COD, NANTUCKET or NORTH CALIFORNIA can result in a SEVERE hemolytic anemia?
Babesiosis
What diarrheal illness can cause hemolysis due to its toxin?
Clostridium sepsis
In South America (Brazil, Peru, Argentina, Venezuela, etc.), a SAND FLY can cause this disease that can result in SEVERE, RAPID, life-threatening hemolysis?
Bartonellosis (Oroya fever)
What is the principal molecule that regulates IRON homeostasis and is made in the liver?
HEPCIDIN (decreases iron absorption from the intestine and inhibits iron release from macrophages)
What special molecule made in the liver that regulates IRON homeostasis is LOW in HEMOCHROMATOSIS thereby causing a much higher intestinal absorption of iron? What gene is affected?
Hepcidin; HFE gene
Cardiomyopathy, Arrhythmias, ELEVATED LFTs, Cirrhosis and HCC, DM, Arthropathy and BRONZING of the skin?
Hemochromatosis
What is the best TEST to evaluate for HEMOCHROMATOSIS other than genetic testing for HFE gene mutation?
Serum TRANSFERRIN >60% (or Ferritin >1000 IF NO INFLAMMATORY STATE), can do liver biopsy if needed
How is HEMOCHOMATOSIS treated?
Like Polycythemia Vera, by PHLEBOTOMY, maintaining serum FERRITIN levels
Why is it important to diagnose HEMOCHROMATOSIS early?
Because can prevent cardiac, liver, DM pathology if treatment starts early, once disease affects these organs, it will not be reversible
In patients with IRON overload from frequent transfusions, what is used to treat?
DEFERASIROX (NOT phlebotomy)
What is the BEST choice of blood transfusion type to be given in an EMERGENCY when no information is known abut the recipient’s blood type?
Type O-negative (negative refers to the Rh(D) antigen)
What is the ONLY true indication for erythrocyte transfusion?
To INCREASE the OXYGEN-carrying capacity of blood
What should be the transfusion Hb threshold in a CRITICALLY ILL patient who is NOT actively bleeding and WITHOUT cardiac compromise?
7 g/dL (if cardiac compromise, 10 g/dL)
What does LEUKOREDUCTION do to a blood transfusion?
Removes leukocytes decreasing HLA alloimmunization (alloantibodies), reduces FEBRILE non-hemolytic transfusion reactions and decreases CMV transmission
For planned intracranial surgery, what must the platelet count be above prior to warranting a platelet transfusion?
> 100,000/µL
What is the combination of Factor VIII, Fibrinogen, von Willebrand Factor (vWF) and Factor XIII called?
Cryoprecipitate (a transfusion for hypofibrinogenemia, Factor XIII deficiency and Hemophilia A or von Willebrand disease)
What patients warrant use of Erythropoietin Stimulating Agents (epoetin and darbaportin)?
Those with kidney disease associated anemia and those with malignancy associated anemia
What is the danger with the use of Erythropoietin Stimulating Agents (epoetin and darbapoetin) and what should be the Hb limit when used?
High risk for thrombosis; limit use to a Hb of 11 g/dL
When a patient receives a PLATELET transfusion and becomes alloimunized to Human Leukocyte platelet Antigens (HLA), especially HLA-I Ag, what happens?
They become REFRACTORY to future PLATELET transfusions, requiring HLA MATCHING
ONE single-donor platelet unit is the SAME as SIX pooled random-donor units and would provide how many platelets?
20,000-30,000/µL
Platelet Transfusions carry a higher risk of bacterial infection and sepsis than compared with other blood products (kept at room temperature), what is the most common infectious agent?
Staph. aureus
In a patient with Leukemia, without other risk factors and no active bleeding, at what level of platelets would a platelet transfusion be recommended?
≤10,000/µL
