Περίπτωση 3 Ένας 66 χρονος άστεγος διακομίζεται λόγω γενικευμένης σύγχυσης, αναφέρεται πτώση από σκάλες Στη φυσική εξέταση υπάρχει ουλή λαπαροτομής στην κοιλιά. Ht 24 Hb 7.8 MCV 108 WBC 2.000 PLTs κ.φ
Liver Fe = 3.7-6.8% d wt Heart Fe = 0.6 –1.3% d wt Thyroid Fe = 1.6 – 6.8% d wt Pancreas Fe = 1.4-3.9% d wt Adapted from Modell & Berdoukas, 1984 Tissue Iron Concentrations in Transfusion- dependent Thalassemia Patients
Τι έχει συμβεί στην ασθενή ? Σπληνεκτομή – Howell Jolie
Περίπτωση 7 άνδρας 28 ετών με HIVδιακομίζεται στα Ε.Ι λόγω αλλαγής του επιπέδου συνείδησηςΘερμοκρασία 39.2 wbc 4.2, ANC 2200, hgb 7.2, mcv 80, rdw 18, platelets 52K, creatinine 3.2, LDH 4200, bili 2.2
Case 4 68 yo white female with a 10 year history of poorly controlled type II DM, HTN, CAD presents for routine follow-up. CBC: wbc 7.2 with normal diff, hgb 9.8, hct 28, mcv 82, rdw 11, platelets 252K BMP: creatinine 3.4
Case 7 72 yo female with no significant PMH is brought for a routine physical by her daughter She has not seen a doctor in 20 years Daughter notes that mom is increasingly tired and has abdominal distension On exam, patient is pale and has marked splenomegaly CBC: wbc 4.2, hgb 7, hct 20, mcv 94, platelets 72K
Megaloblastic anemia: Morphology--Blood Peripheral blood –Macro-ovalocytes –Neutrophil nuclear hypersegmentation Very sensitive and specific Normal Megaloblastoid
Cabot ring - Ring shaped, thin - May be figure of 8 shaped - Microtubule, remnants of of the mitotic spindle - Rarely seen Howell Jolly body - Round, dark, refractile RBC inclusion - Nuclear remnant - Most commonly seen in hyposplenism Basophilic stippling - Multiple small blue dots dispersed regularly throughout the RBC - RNA complexes
Autoimmune Hemolytic Anemia Result from RBC destruction due to RBC autoantibodies: Ig G, M, E, AResult from RBC destruction due to RBC autoantibodies: Ig G, M, E, A Most commonly-idiopathicMost commonly-idiopathic ClassificationClassification –Warm AI hemolysis:Ab binds at 37degree Celsius –Cold AI Hemolysis: Ab binds at 4 degree Celsius
1.Warm AI Hemolysis: –Can occurs at all age groups –F > M –Causes: 50% Idiopathic50% Idiopathic Rest - secondary causes:Rest - secondary causes: 1.Lymphoid neoplasm: CLL, Lymphoma, Myeloma 2.Solid Tumors: Lung, Colon, Kidney, Ovary, Thymoma 3.CTD: SLE,RA 4.Drugs: Alpha methyl DOPA, Penicillin, Quinine, Chloroquine 5.Misc: UC, HIV
Direct antiglobulin test demonstrating the presence of autoantibodies (shown here) or complement on the surface of the red blood cell. complement
Inv:Inv: –e/o hemolysis, MCV –P Smear: Microspherocytosis, n-RBC –Confirmation: Coomb’s Test / Antiglobulin test TreatmentTreatment –Correct the underlying cause –Prednisolone 1mg/kg po until Hb reaches 10mg/dl then taper slowly and stop –Transfusion: for life threatening problems –If no response to steroids Spleenectomy or, –Immunosuppressive: Azathioprine, Cyclophosphamide
2. Cold AI Hemolysis –Usually Ig M –Acute or Chronic form –Chronic: C/F:C/F: –Elderly patients –Cold, painful & often blue fingers, toes, ears, or nose ( Acrocyanosis) Inv:Inv: –e/o hemolysis –P Smear: Microspherocytosis –Ig M with specificity to I or I Ag
Other causes of Cold Agglutination:Other causes of Cold Agglutination: –Infection: Mycoplasma pneumonia, Infec Mononucleosis –PCH : Rare cause seen in children in association with cong syphilis
Treatment:Treatment: –Treatment of the underlying cause –Keep extremities warm –Steroids treatment –Blood transfusion
Non-Immune Acquired Hemolytic Anemia 1. Mechanical Trauma A). Mechanical heart valves, Arterial grafts: cause shear stress damage B).March hemoglobinuria: Red cell damage in capillaries of feet C). Thermal injury: burns D). Microangiopathic hemolytic anemia (MAHA): by passage of RBC through fibrin strands deposited in small vessels disruption of RBC eg: DIC,PIH, Malignant HTN,TTP,HUS
Acquired hemolysis 2.Infection F. malaria: intravascular hemolysis: severe called F. malaria: intravascular hemolysis: severe called ‘Blackwater fever’ Cl. perfringens septicemia oxidant denaturation of hemoglobin 3.Chemical/Drugs: oxidant denaturation of hemoglobin Eg: Dapsone, sulphasalazine, Arsenic gas, Cu, Nitrates & Nitrobenzene
The direct antiglobulin test was positive for complement (C3d) (++), and IgG (++-). Also was positive for agglutinins of IgM type and had a titer of 1:1024.
Serologies for human immunodeficiency virus, hepatitis B and C viruses, and Mycoplasma pneumoniae were negative. Rheumatoid factor and antinuclear antibodies were undetectable.
Prednisone therapy was started at a dose of 1 mg/kg intravenously, daily. Hemoglobin level rose to 11 g/dL, concomitantly with the improvement of hemolytic signs.
A reduction of positivity of both direct and indirect antiglobulin tests (polyvalent serum + ; C3d + ; IgG+ ), as well as a reduction of cold agglutinin titers (1:128), was observed 8 weeks after corticosteroid therapy.
Three months later, corticosteroids were tapered to a maintenance dose of 25 mg daily. Hemolysis recurred again with the fall of hemoglobin to 7 g/dL.
The direct antiglobulin test recurred positive for polyvalent serum (+++), complement (+++), and IgG (+++), while cold agglutinin titers again became strongly positive (1:256).
Immunophenotyping of bone marrow cells showed that 10% of all the cells were CD20 and CD19 positive.
CD20 is widely expressed on B-cells. CD20 could play a role in Ca2+ influx across plasma membranes, maintaining intracellular Ca2+ concentration and allowing activation of B cells.
Rituximab is a monoclonal antibody that binds to CD 20 Rituximab was started at the dose of 375 mg/mq once weekly, for a total of 4 doses
Hemoglobin value reached 13.5 g/dL just before the third dose, although biochemical signs of hemolysis remained substantially unaltered.
At the end of therapy, the hemolytic signs disappeared, the direct and indirect antiglobulin tests became negative, and cold agglutinin titers fell to 1:32 Immunophenotyping of bone marrow cells showed the absence of CD20 and CD19 B cells.