Plasma Cell Tumors or Multiple Myeloma or Myeloma Cells

Plasma Cell: it is a mature form of B cell present in bone marrow and lymph nodes as solitary cells but not present in circulation. Characteristics: 1. Urine analysis produces Bence Jonce proteins which precipitate during heating and redissolve upon cooling. (immunoglobulin molecules are incompletely formed) # of light chains > # of heavy chains unattached light chains appear in urine as Bence Jonce protein The production of IgM is uncontrolled (heavy production) Light chains may pass through capillaries causing damage to many organs including the kidney. 2. Protein electrophoresis: produces a narrow acute band of y-globulin. 3. Radiology: produces lakuna in bones as plasma cell causes activation of osteoclasts that may lead to bone fracture. 4. Bone marrow puncture (naps of plasma cells) : normally present as solitary cells 5. Hypercalcemia, hyperphosphatemia: due to action of osteoclasts 6. Hyperuricalcium, hyperuriphosphorus and renal stones 7. Renal failure 8. Gout: due to high turnover of cells high amount of nucleic material high uric acid production gout 9. Blood picture : anemia, thrombocytopenia, leukopenia ----------------------------------------------------------------------------------------------------------------------------

Major Host Compatibility Complex Human Lymphocyte Antigen (MHC HLA)

Methods of development of antibodies (Anti-HLA): 1. Immunization through blood transfusion Amount of Abs increases by increasing transfusion. i.e. one time transfusion may not develop antibodies but a significant amount is formed by 5-10 transfusion times. 2. Pregnancy (gestation) First baby contains HLA from the father. During labour, baby's blood and mother's blood mix producing antibodies by 10%. Every labour after that increases Abs by 10 % reaching 50% after 5 labours. 3. Transplantation especially bone marrow transplantation. Consequences of immunization by HLA (clinically) especially by blood transfusion: If blood is transferred from one donner to recipient, this will lead to formation of antibodies against HLA. By second transfusion, Ag-Ab rxn. appears as tremors, fever, headache, lowering blood pressure, dyspnea, acute pulmonary oedema which may lead to death. If transfusion is continued, lumber pain results due to hemolysis which affects the kidney. How to solve this problem? Change donner or use deleukocyted blood.

Bone Marrow Transplantation Use chemotherapy and radiation to suppress the immune system. Immune system can't be suppressed completely. This may lead to: 1. Rejection Macrophage recognizes foreign cells stimulates T-Helper cells activates B cells formation of Abs Ag-Ab complex complement activation cell lysis activates T cytotoxic cells cell lysis Both of these pathways lead to rejection. 2. Graft Versus Host (GVH) rxn: The grafted cells survive and react against the host cell (instead of rxn of host against the graft, the reverse rxn occurs). This may lead to death. This rxn is done through Class II, macrophages, T-helper and B cells. All lymphoid tissues are involved eg. Langerhans, peyers patches in intestine, spleen, lymph nodes in the body. Clinically: Hepatospleenomegaly, adenopathy, skin rashes, diarrhea, fever and weight loss leading to death take place. To overcome this problem, mixing cell culture must be done. Mixing Cell Culture = Cross matching rxn (Blood group ABO)
Lymphocytes of the donner + lymphocytes of the receiver (which is inactive) + thiamine radioactive (enters in nucleic acid)

The donner cells must be activated and converted to lymphoblasts and divided taking up radioactive thiamine. Under the microscope large # of lymphoblasts (20-25 microns) and measure radioactivity. If it is high, this means cell division is taking place. Therefore, lymphocyte activation has occurred. So transplantation is not done. NB. After transplantation, the patient must be guarded against infection especially against cytomegalovirus because the virus enters the cell and changes HLA the cell becomes foreign leading to rejection rxn (i.e. HLA may be matched and rejection occurs)

Biological Survey of Pregnant Woman (RH- of her newborn) Why we do this? (i.e. Purpose) 1. Evaluation of immunization risk and its severity 2. Prediction of fetal injury 3. Orientation of therapeutic protocol before and after labour 4. Irradication of possible immunization of the mother RH- by anti-D A) Survey for NON-IMMUNIZED Pregnant woman (i.e. not exposed to RH+ and she is RH-) i. During Pregnancy a) Interrogation: Previous blood transfusion or obstetric problem? b) Biological Survey A) Blood Grouping: A,B,O Rh(D,Cc,Ee) Kell B) Searching for irregular agglutinin (SIA): This woman may have Ab against D,Kell,... So by Indirect Coomb's Rxn.: Ab of mother's serum + kits of different Bd group Ags on sensitized RBC by pepsin or papain enzyme + anti-Ab of mother's serum: Rxn. Present woman has Ab(D,Cc,Ee,....) SIA +ve identify Ag type check for the consent of that Ab by making dilution of Ab and take the positive aggregation of the last one Rxn. Not present woman is good SIA -ve no risk on fetus NB. For SIA negative mother Avoid any trauma to the pregnant woman as it facilitates the passage of RBCs of the fetus into the mother's circulation. Causes of trauma: A) Biopsy of trophoblast B) Aminocyntasis (i.e. withdrawing a sample of the amniotic fluid) C) Collecting blood sample of the fetus D) Any mechanical trauma in the uterus Under these circumstances, Anti-D Ab must be taken. ii. After Labour a) Immuno-hematology Exam A) Umbilical blood sample searching for Rh,A,B,O...etc. B) Direct Coomb's test (as the fetus may be sensitized during pregnancy) C) Searching for irregular agglutinin in mother's serum

B) Survey for IMMUNIZED Pregnant Woman Rh- (i.e. she has Ab against Ec,Cc,D) Purpose: Follow up of gestation of pregnant woman to avoid fetal death due to anemia After labour risk of jaundice

i. During Pregnancy 1. Interrogation: previous transfusion or obstetric problem Take into consideration: 1. The probability of formation of Ab increases with the number of labours 2. The risk of fetal death reaches 80% after the first labour 2. Biological Diagnosis during pregnancy 1. Prediction of alloimmunization (maternal immunization SIA, Ab against D) 2. Prediction of fetal affection 1. Phenotyping of Rh group of father (Genotype and Phenotype) D D Father d d Mother Both will be Dd positive D d Father d d Mother 50% of kids will be positive and the other 50% will be negative 2. Analysis of Ab evolution in the mother 1. Indirect Coomb's test is done to mother's blood qualitatively (= titrage) and quantitatively Allowed: Titer Not more than 1/8 IF >1/8 +ve IF < 1/8 -ve Concentration of Ab (anti-D) = 1 mg/ml Possibilities: a) If indirect Coomb's <1/8 , < 1 mg/ml Weak activity of Ab and weak concentration no risk on fetus b) If indirect Coomb's <1/8 , > 1mg/ml Weak activity of Ab but high concentration no severe effect on fetus c) If indirect Coomb's >1/8, < 1 mg/ml High affinity but low concentration no severe effect on fetus d) If indirect Coomb's >1/8, > 1 mg/ml High affinity and high concentration severe effect on fetus

3. Study of Amniotic fluid 4. Take a blood sample from the umbilical cord of the fetus in the 20th week but not before that WHY?? a) To detect the hemoglobin concentration (levels: allowed till 15 gm/dl and may reach 5 gm/dl but transfusion should start if <7 gm/dl) b) To detect bilirubin in blood (remove as much as bilirubin as possible from his circulation) HOW to detect bilirubin?? By reading optical density using spectrophotometer at 450 nm according to the table detect severity of jaundice. N.B. Bilirubin causes thickness of the umbilical cord leading to the cutting of blood supply to placenta and fetal death 5. ECHO is done regularly To detect level of anemia and blood hemolysis which leads to: 1. Ascites 2. Thickening of the umbilical cord 3. Oedema ii. After labour 1. Blood of umbilical cord withdraws very low hemoglobin (<15 gm/dl) 2. Bilirubin elevates to 12 mg/dl (normal 1 mg/dl) 3. Signs of RBC regeneration High reticulocytosis (> 10-15%) Erythroblastosis leading to leukocytosis Low platelet count and hemorrhage N.B. Reticulocytosis occurs due to a great increase in RBC count which mature very quickly so reticulocyte count increases to compensate for that. Some kids may be born with hemolytic anemia regardless the Rh story.