Treatment of anemia

bleeding (ulcers , hemorrhoids , inflammatory bowel diseases, some parasitic diseases eg bilharzia and Encylostoma)
2-Decrease iron absorption as in cases of mal-absorption syndrome or drugs (tetracycline , phosphate , phytate (bran), antacids , drugs that decrease gastric HCl secretion in patients with peptic ulcer )
3-Increase iron demands as in cases of
Delayed weaning of children because breast milk is deficient in iron .
Pregnancy.
Premature baby due to decrease iron stores derived from the mother
During treatment of pernicious (vitamin B12 &folic acid deficiency) anemia due to excessive formation of new RBCs .
Clinical picture of anemia
1-Decrease RBCs leads to fatigue, pallor in skin and mucous membranes.
2-Deficiency in iron containing enzymes leading to degeneration of mucous membrane in tongue (glazed tongue with loss of papillae )tonsils and atrophy of epithelial cells in skin and GIT .
3-Decrease immunity leading to increase susceptibility to infections. especially helminthic infections.
Indications of iron therapy
Iron deficiency anemia.
Prophylactic against iron deficiency anemia as a result of increased iron demands (pregnancy and premature babies).
During treatment of other causes of anemia (increase iron demand as a result of excessive formation of new RBCs.)
Preparations of oral iron
-Ferrous sulfate contains 60 mg of iron/tablet.
- Ferrous fumarate contains 65 mg of iron/table.
-Ferrous gluconate &succinate contains 35 mg of iron/tablet.
-Ferrous editate and elemental iron .They are tasteless .They are used to fortify milk.
Dose:200 mg (2tablets three times daily) or 2-3 mg/kg for adults and 5mg /kg for children .it increases HB by 0.2 g/day .
-Iron should be administrated till serum hemoglobin is normalized followed by1-2 months to replenish iron stores.
-If there is continuous iron loss ,administrate iron in a dose of 20 mg /6 hours till the cause of iron loss is treated.
-Drugs that increase iron absorption :Acids ( vitamin c , citrates , succinates) , sulfur containing amino acids (SH group reduces ferric to ferrous ions) are combined with iron therapy.
Side effects
1-Dose dependent due to direct effect of iron :nausea ,vomiting and upper GIT upset.
2-Dose independent due to decrease bacterial flora :indigestion ,diarrhea or constipation
.

iron therapy.
2-Malabsorption syndrome as in cases of inflammatory bowel syndrome or surgical resection of large part of intestine.
3-When iron deficiency should be compensated rapidly as in cases of pregnancy or before surgical operations.
Preparations of parenteral iron-Iron sorbitol .It is rapidly absorbed .It can be given both intravenously and intramuscularly.
-Iron dextran .It is slowly absorbed. It can be given slowly intravenous or intramuscular
Dose of parenteral iron: Total dose of iron =iron deficit in grams X 250 or deficit in % X 3 X body weight. It is administrated intravenous infusion in 5% glucose solution (maximal concentration is 2.5 g iron /liter.
Initial test dose 0.0.5 ml of the solution is first administrated over 3 minutes to test for of anaphylactic shock.
-Intramuscular iron is administrated by Z technique (move skin upwards before injection)to avoid skin staining. It may cause sarcoma at the site of injection
Side effects of parenteral iron:
Systemic: Anaphylactic shock ,Headache and Lymphadenopathy.
Local :tissue staining and malignancy (sarcoma at the site of IM injection).
 Acute iron toxicity
-Due to suicidal or accidental intake of large doses of iron .It is manifested by
GIT manifestations : vomiting ,abdominal pain and bloody diarrhea.
Cardiovascular manifestations : Metabolic acidosis ,collapse
CNS manifestations : coma and convulsions
Hematological :hemolysis.
Treatment
-Decrease iron absorption by:
Administration of milk or row egg white.
Gastric lavage by alkaline solution eg 1% sodium bicarbonate .
Iron chelating agents 5 g desferroxamine infusion is left in the stomach after gastric lavage.
-Chelating plasma iron by desferroxamine 1-2 g intramuscular or 15 g/kg intravenous.
-Correct acidosis by intravenous infusion of alkaline salt (sodium bicarbonate or 1/6 molar sodium lactate).
Chronic iron toxicity (hemochromatosis):-Due to congenital defect in iron absorption or repeated blood transfusion in patients who do not bleed (agranulocytosis or severe anemia).
-It is manifested as tissue iron deposition , liver cirrhosis , heart failure , impotence and hemolytic anemia).
Treatment :-Repeated venesection 500 ml /week.
-Iron chelating agents :intramuscular desferoxamine 1-2 g/day .
NB: iron therapy and iron rich dietary products are contraindicated in liver diseases due to iron induced hepatotoxicity.

hydolase

H+ Dihydrofolic acid mono-glutamate

Dihydrofolic acid mono-glutamate-binding protein in plasma

Di-hydro-folic acid in tissues

Folate reductase enzyme

Tetra-hydrofolic acid

Active N -methelene tetra-hydro-folic acid

Vitamin B12

Homosystine (methyl donor)

systothionine

Uracil

thymine

DNA

Krepe s cycle

Succenyl coA

Methylmalonyl CO A

Odd number fatty acids

Myline sheath

Rapidly dividing cells

Causes of vitamin B12 deficiency
1-Decrease GIT absorption : *Mal-absorption syndrome,
*Drugs ( metformin (antidiabetic ) , nitrous oxide , drugs that reduce gastric HCL in treatment of paptic ulcers )
*Surgery that removes part of stomach or small intestine (obesity surgery)
*Decrease synthesis of intrinsic factor :congenital , stomach diseases (atrophic gastritis, cancer stomach)
2-Increase consumption : *Parasitic infections (diphylobotherium ).
*Increase demand during treatment of other forms of anemia
3-Decrease synthesis by intestinal flora: long term use of broad spectrum
antibiotics which inhibit commensals and increase fungi which consumes
vitamin B12

Causes of folic acid deficiency
1-Decrease absorption:-Mal-absorption syndrome & antiepileptic drugs (phenytoin & barbiturates ), ethanol
2-Increase demand: pregnancy, treatment of other forms of anemia
3-Impaired activation by vitamin B12 in vitamin B12 deficiency
-Folate reductase inhibitors (trimethoprim , anticancer(methotroxate , 5flurouracil ), antiviral ( acylovir , zidofudine), anti-protozoal (Pentamidine, pyrimethamine) ,
Diuretic (triametrine)

Homocystine methyl transerase

Antiepileptic drugs :phenytonin , barbiturates ) , ethanol , antacids
drugs of peptic ulcer treatment

-

Metformin , nitrous oxide , ethanol , drugs that reduce gastric HCl in peptic ulcer treatment

-

Folate reductase inhibitors :anticancer drugs(methotroxate) ,5fluro-uracil, trimethoprim , pentamidine , zidofudine , acyclovir , diuretic (triametrine

-

Intestinal epithelium

Active transporter

P-glycoprotein

deficiency in combination with vitamin B12 in order to activate folate
2-Prophylactic in conditions associated with increase folate demands in cases of :
Pregnancy .It may reduce the risk of congenital anomalies of nervous system.
Premature babies
During treatment of other types of anemia (hemolytic anemia ) due to active bone marrow
Treatment of drugs that interfere with absorption or activation of folic acid .
3-Poor intake of folic acid (old age , severe illness , starvation or prolonged malnutrition or poor appetite in depression
4-Bleeding hypertrophied gum : folic acid is required for activation of metalloprotease and collagenase enzymes required for collagen turnover in gums and other tissues
Preparations of folic acid
Dihydrofolic acid (FH2) 3 times/day. It is given orally .It needs activation to methylated tetrahydrofolic acid by vitamin B12.
- Active Follinic acid (formyl tetrahydrofolic acid)is used in combination with folate reductase inhibitors to prevent anemia.
Side effects of folic acid preparations
1-Allergic reactions (skin rash , bronchospasm , itching) due to hypersensitivity reactions to drug solvents.
2-Very large doses may cause gout due to increase formation of nitrogenous bases which are metabolized to uric acid.
3-Large doses of folic acid alone in pernicious anemia caused by either deficiency of folate or vitamin B12 may cause consumption of vitamin B12 in activation of folic acid and appearance of nervous side effects of vitamin B12 deficiency

Therapeutic uses of vitamin B12(hydroxycobalamine & cayanocobalamine )
1-Treatment of vitamin B12 deficiency anemia initial dose of 1000 ug /month till the blood picture is normalized then it is administrated in a dose of 1000 ug /1-3 months for life.
2-In combination with folic acid in treatment of folic acid deficiency anemia to promote folic acid activation.
3-Treatment of peripheral neuritis and degenerative conditions of nervous system mediated by vitamin B12 deficiency .
4-Treatment of cyanide poisoning: IV hydroxycobolamine binds CN- to forms non toxic urinary excreted cyanocobolamine
Preparations :Usually it Vitamin B12 is used IM to bypass slow GIT absorption and intrinsic factor deficiency. Oral preparations are used in combination with desiccated (dried ) gastric extract that contain extrinsic factor to promote absorption. IV preparations are used in treatment of cyanide poisoning.
1-Hydroxycobolamine is IV or tablets. It is the only preparation used for treatment of cyanide poisoning.
2-Cyanocobolamine oral and IM .It is cheap
NB: Ethanol increases GIT iron absorption but decrease its utilization it decreases folic acid , vitamin B6 & vitamin 12 absorption. It may cause megaloplastic (Folate or vitamin B12 deficiency) anemia, microcytic anemia due to vitamin B6 deficiency or defective iron utilization.

and cause oxidative damage to cell membrane of RBCs
-Paracetamol , sulfonamides , primaquine ,, ascorbic acid , methelene blue, iron , vitamin k .

Autoimmune mediated hemolytic anemia:
Drugs binds to cell membrane of RBCs and change its structure leading to activation of immune system which form anti-RBC cell membrane autoantibodies
Antibiotics , penicillins ( pipracellin) , fluoroquinolones (levofluoxacin &nalidexic acid) , nitrofurantoin
Anticancer drugs : fudrapine
Antiinflammatory drugs :NSAIDS (declofenac ) , dapsone
Antihypertesive drugs ; alpha methyldopa.
Antiparkinsonian drugs : L-dopa
Antiarrhythmic drugs: quinidine.
Phenazopyridine (pyridium): urinary tract analgesic

Diagnosis of autoimmune hemolytic anemia

Treatment of drug induced hemolytic anemia

1-Stoppage of causative agent
2-Non specific supportive therapy used in any case of hemolytic anemia
In acute hemolysis
-Fresh warm blood transfusion . Cold blood is not used because it may activate cold agglutinins which aggravate hemolysis. Give the lowest possible dose (500-1000 ml )at rate 1ml/kg/hour.
In between attacks
-Iron chelating agents (IV desferoxamine ) or Deferasirox, defriprone (low molecular weight) agents to prevent deposition of iron released from hemolysed RBCS. Dferasirox (90 mg tablets) 20 mg /kg once daily and defriprone (100 mg /ml oral solution) 25 mg /kg TDS better than desferoxamine being low molecular weight which allow it to chelate intracellular iron.
-Erythropiotin is a cytokine secreted by the kidney in response to cellular hypoxia it stimulates RBC production in the bone marrow. It is used in hemolytic anemia (sphirocytosis & associated with reticulocytopenia) to decrease requirement for transfusion
-Iron therapy is contraindicated because iron released from hemolysed RBCs is reused except there is low serum iron

mg (1/2 -1 vial IV infusion for 3 days followed by oral prednisolone 1-1.5 mg /kg till HB reaches 10g/l
2nd line
1-Ritoximab : monoclonal antibodies against surface protein antigen (CD20) of B lymphocyte. It suppresses B cell mediated immunity. Side effects are increase susceptibility of infection , renal failure due to blockade of renal tubules by proteins released from destroyed B lymphocytes ,acute infusion reaction resulted from infusion of foreign proteins& release cytokines from lysed WBCS causing cardiac arrest , hypotension and tolerance due to formation of antibodies. Dose 1000 mg in 100 ml solvent slowly IV
2-Low dose Immunosuppressive agents : azathioprine (100-150 mg /day), cyclophosphamide(100 mg/day) .They inhibit immune reaction by inhibition of proliferation of lymphocytes.
3-Danazole alone or (200-400 mg /day) in combination with cortiosteroids .
4-IV immunoglobulins (2g/kg ) They may interact with pathogenic antibodies or block Fc receptors in macrophages.
5-Exchange transfusion or plasmaphoresis
3rd line
1-High dose cyclophosphamide 50 mg /kg /day for 4days followed by granulcytic colony stimulating factor
2-Alemtuzumab, a humanized monoclonal antibodies against CD52 of lymphocytes (highly toxic)
3-Hemopiotic stem cell transfusion

Complement induced hemolytic anemia:
1- Ecluzimab: complement C5monoclonal antibodies. It blocks autoimmune reaction by blocking complement activation. Dose 600-900 mg (2-3 vials ) slow IV infusion
Side effects are similar to ritoximab.
2-Anabolic steroids or danazole (200-400 mg day oral )It induces expression of Complement C1 esterase inhibitor which inhibit complement pathway of immune reaction

sickle cell (HBS) anemia Hydroxyurea which liberate nitric oxide which stimulate production of hemoglobin F which is less toxic and does not precipitate in acidic medium as hemoglobin s which causes sickle crisis. Other uses:
-Polycythemia, thrombocytosis, leukemia) & malignant tumors because it inhibits ribonucleotide reductase responsible for formation of desoxyribose required for DNA synthesis
Dose :oral 40 mg /kg (2 capsules) TDS reduced by 50% after improvement
Side effects :renal failure , depression of rapidly dividing cells (bone marrow , gonads, skin & mucous membrane ).

Splenectomy
For extra-vascular and autoimmune hemolytic anemia

antineoplastic agents , immunosuppressants and biogenic slow acting disease modifying antiinflammatory drugs , interferon alpha
Some antimicorbial : chloramphicol , flurocytosine , dapson.
Colcichine : inhibits mitotic spindles
B-Free radical formation :
Benzene and benzene containing substances: kerosine , carbon tetrachloride , insecticides (parathion , landane) because they are metabolized in the liver to hydroquinones and free radicals which directly stimulate apoptosis and destroy bone marrow stem cells

II-Dose independent ,immune or idiocyncrasy mediated
(rapid onset & unpredicatable ):
Antimicrobial :chloramphicol , dapson
Antiinflamamtory : Indomethacine , penicillamine
Antiepileptics : carbamazipine , phenytoins, primidone
Heavy metals : gold , arsenic ,
Antiarrhythmic : quinidine , procainamide ,tocanamide
Antithyroid drugs: thiurea , potassium perchlorate
Antihypertensives : captopril , methyldopa , enalpril
Antipsychotics : chlorpromazine , prochlorpromazine
Hypoglycemic agents : Sulfonylurea (chloropamide)

Drug induced aplastic anemia

Drug induced agranulocytosis :Granulocytes below 200 cells/mm

Isolated neutropenia

Isolated eosinopenia

Isolated basopenia

The same drugs that produce aplastic anemia + valproic acid (antiepileptic) ,mianserin , miretzapine ,(antidepressants ) , clozapine (antipsychotic) ,benazipril (antihypertensive ) , dipyrone , naproxyne (analgesic), allopurinol ( antigout) , benzimidazole (antiparasitic) , vancomycin & sulfonamides (antibiotics) , defireprone (iron chelating agent),sulfasalazine , cimetidine , ranetidine (H2 blockers).

Drug induced thrombocytopenia

The same drugs that produce agranulocytosis +abciximab , tirofibran (antiplatelet) , danazole , refampicin (antibiotic)

cells

Meyloid progenator cells

Granulocyte , monocyte colony stimulating factor &IL 1&3&6

Monopotent blast cells

Monopotent blast cells

Pro-lymphocytes (blast cells)

IL1&7&12&TNFa
TGFB1 ,Small cell
derived factor-1

Pro-myelocytes (blast cells)

Granulocyte , monocyte colony
stimulating factor &IL 1&3

Lymphocytes

IL 1&2&4&6&7

Reticulocytes

Erythropiotin
Iron , trace elements &vitamin B1 &B6

Thrombopiotin
IL6 &IL11

Megacaryocte

Platelets

RBCs

Granulocyte & monocyte colony stimulating factor
IL3 &6

Granulocytes

Monocytes

Vitamin B12 &Active folic acid
Increase nitrogenous basis
required for cell division

Hematopoisis &Hemopiotic growth factors

mature RBCS)
It is used in cases of
-Aplastic anemia
-Hemolytic anemia to reduce exogenous blood transfusion
-Anemia due to renal failure to replace renal secretion of endogenous erythropoietin
-In doping to increase physical fitness of athletes
-Autologous blood transfusion: before surgical operations .
Side effects :-Immune reaction caused by injection of foreign protein :flu like symptoms , skin rash, itching
-Headache , hypertension ,thrombosis due to increase blood viscosity as a result of excessive RBC production
-Sternal bone pain due to bone marrow expansion.
-Iron deficiency anemia as a result of excessive RBC formation.
-Antibody formation leading to tolerance (pure red cell aplasia).
Preparations :
Recombinant Short acting preparations :Erythropoietin (epeotin a ) is injected sc or IV 3 times / week
Long acting preparations :pegylated epeotin B & polyglycosylated erythropioin(darbipeotin): once /1-4 weeks

Erythropoietin

RBC specific hematopoietic growth factors

of thrombopoietin (platelet activating hormone)
-It stimulates differentiation of megakaryocytes to platelet through JANUS /mitogen activated protein kinase pathway.
-It is used in treatment of thrombocytopenia
-It is injected SC 1ug/kg /week until platelet Count is over 50,000 then reduce the dose Gradually and stop drug if platelet count is Over 150,000 /mm
-Side effects :- Thrombocytosis , thrombosis
-Bone marrow fibrosis due to increase collagen and reticulin formation in bone marrow by activation of I3K pathway of cell division , anemia ,
-Ischemia , myalgia

2-Oprevakin: recombinant IL11.
-It stimulates differentiation of megakaryocytes to mature platelets , healing of endothelium and intestinal epithelium , inhibition of adepogenesis
-It is used in treatment of chronic thrombocytopenia due to chemotherapy , liver cirrhosis or malignancy
-Dose is 25–50 μg/kg per day sc 1day before chemotherapy and discontinued 2 days before next cycle of chemotherapy. It is stopped if platelet count reach 50000/mm
Side effects:-Allergic reaction , itching , bronchospasm , hypotension
-Fluid retention duo to:
1- Direct effect of drugs on sodium reabsorption from renal tubules
2-Capillary leak syndrome (differentiation syndrome) resulting from release of cytokin from proliferative myelocytes.This leads to:
Hyertension , headache , systemic and pulmonary edema heart failure .
Blurring of vision ,optic disc edema
Atrial arrythmia due to sodium retention and increase blood volume.
-Increase cortical bone thickness due to stimulation of osteogenesis
-Teratogenic

NB; thrombopoietin is not used clinically due to rapid development of tolerance.

3-Eltrombopag
-Orally active small molecular weight thrombopoietin receptor agonist. It stimulates STAT but not Akt pathway. It does not cause fluid retention. Side effects are GIT upset , allergic reactions , flu like symptoms , myaligia , sore throat , .
-Dose is one tablet (50 mg ) 4 times daily

is used for treatment of
Chemotherapy induced agranulocytosis. They are commonly used in acute myeloid leukemia. The drugs are administrated 4days after completion of chemotherapy cycle and continued till neutrophils becomes more than 500/mm3 . They are not used 1 day prior or after chemotherapy
Prior to stem cell transplantation in order to increase peripheral stem cells
Radiation induced and idiopathic agranulocytosis.The drugs are given as early as possible .
To stimulate bone marrow after bone marrow transplantation.The drugs are administrated immediately after bone marrow transplantation.
Aplastic anemia
-Side effects:
Bone pain
Local pain at the site of injection
Allergic reaction : itching ,edema , hypotension probably mediated by drug solvents
Rupture spleen
Bleeding (hemoptosis , alveolar hemorrhage).
Precipitation of sickle crisis in patients with sickle cell anemia
Preparations
Short acting preparation:
1-Filgrastim (300 mcg vial )is administered by subcutaneous injection or intravenous infusion over at least 30 min at doses of 1–20 μg/kg/d once /day .
2-Sargramostim (500 mcg / ml vial) : 250 mcg /m2 over 4 hours or subcutaneous 4 times daily
Long acting : -Pigylated filgrastim 6 mg sc once /chemotherapy cycle

of all blood cells
1-Non specific general measures
-Blood transfusion in severe acute cases
-Bone marrow stimulants in chronic cases:
*Oral corticosteroids 1-2 mg/kg /day
*Anabolic steroids derived from male sex hormones :Nandrolone decanuate :50 mg IM /month.
*lithium carbonate: 300 mg (one tablet TDS)
Autoimmune aplastic anemia due to autoimmune destruction of bone marrow cells by overactive lymphocytes is treated by
*Antilymphocytic globulins: rabbit or mouse derived antibodies against human lymphocytes.
*Balilximab &Decluzumab: monoclonal antibodies against IL2 receptors on the surface of T lymphocytes .They act by blockade of natural proliferation of lymphocytes induced by interleukin
-They are also used in treatment of organ rejection
-Side effects are similar to ritoximab
Other types of Aplastic anemia caused by drugs (anticancer or antiviral drugs ) ,irradiation cancer therapy cancer or premature babies are treated by:
*General measures:
*Erythropiotin to stimulate RBC production
*Recombinant granulocyte colony stimulating factor to increase WBCS
*Thrombopiotin receptor agonists :Romiplosin to increase platelets

Selective decrease of specific blood cells

Selective decrease in RBCS caused by impaired erythropiotin
Production in chronic renal failure
Treatment: recombinant Erythropiotin (epeotin) is injected sc or IV 3 times / week for Short acting preparations epeotin α once / 1-4 weeks for month for long acting preparations polyglycosylated erythopiotin (darbipeotin) or pigylated(combined with ethelene glycol) epeotin β
-Other uses:-To stimulate bone marrow in cases of autogenic blood transfusion and athletes to increase physical fitness (doping).
-Side effects :-Immune reaction caused by injection of foreign protein :flu like symptoms , skin rash, itching
-Headache , hypertension ,thrombosis due to increase blood viscosity as a result of excessive RBC production
-Sternal bone pain due to bone marrow expansion.
-Iron deficiency anemia as a result of excessive RBC formation
-Antibody formation leading to Tolerance (pure red cell aplasia)

Agranulocytosis : selective deficiency of WBC below 500/mm3
Treatment: -General measures : blood transfusion is less effective due to short life of WBCS & bone marrow stimulants &avoid infections .
-Non immunosuppressive antibiotics : penicillins
-Recombinant granulocyte colony stimulating factor
Short acting :(filgramostim or sargramostim
Long acting piglylated filgrsmin:100 ug sc ,IM ,IV /4 days
Thrombocytopenia is treated by :packed platelet transfusion
-Corticosteroids: prednisolone 1-2 mg /day orally
Thrombopiotin agonists: Romiplostin , orally. Human recombinant thrombopiotin is ineffective due rapid development of tolerance

replace whole blood in cases of hemorrhage.
To replace red blood cells in cases of severe anemia (HB below 8 g/dl) whole or packed RBCS are used
To replace platelets in cases of thrombocytopenia .Packed platelets are used
To replace fibrinogen and clotting factors in cases of hemorrhagic blood diseases .
2-Exchange transfusion : In cases of autoimmune diseases to remove harmful constituents (autoantibodies ) in patients blood by removing blood of patient and replace it with normal donor blood.
3-Doping transfusions : Athletes & military personells undergo blood transfusion to increase their physical capacity before sporting events ,dilute and prevent detection of forbidden drugs in their blood.
Sources of blood transfusion
Autologous :The patient receives his own blood pre-donated before surgery or collected during surgery by special device
Allogeneic (homologous) :Patient receives blood of other person( donor).Persons with O blood group is the most preferable because they can donate their blood to any persons in small amounts because their RBCS contain no A or B antigens
Storage of blood
Blood withdrawn from donor is stored at 4 0C with anticoagulant (3.8%sodium citrate solution) and glucose to provide optimal nutrition to red blood cells. It is expired after 42 days of storage.
Fresh blood : Blood stored for less than 4 days .It provide coagulation factors .
Old blood :Stored for 4 -42 days .It does not provide coagulation factors
Leukoreduced blood: Most of leukocytes are removed from transfused blood by filtration to prevent transmission of intracellular harmful microorganisms (TB , virus) and avoid suppression of immune cells of recipient by donors leukocytes
Packed blood constituents: Packed RBCS and packed platelets are used in anemia and thrombocytopenia to provide required blood constituents and prevent over transfusion

RBCS is precipitated as insoluble acid hematin in acidic media of renal tubules leading to acute renal failure manifested as fever , chills , hematuria and anuria (marked decrease in urine formation below 500 ml /day). It occurs due to:
Acute hemolytic reaction occurs within 24 hours of transfusion due to ABO incompatibility or use of expired blood.
Delayed hemolytic reaction occurs after more than 24 hours of transfusion due to RH incompatibility
Treatment:-Stop transfusion immediately
-Give alkaline salts (sodium bicarbonate or 1/6 molar sodium lactate ) to alkalinize urine.
-Give osmotic diuretic (mannitol IV drip) to prevent anuria.
2-Pyrogenic reaction :It is due to the presence of pyrogens (antigens from dead bacteria) in the apparatus used for blood transfusion. This causes fever and chills. It is treated by- IV hydrocortison semisuuccinate 100 mg IV,10 ml of 10%Calcium gluconate slowly IV drip + H1 blockers (diphenhydramine 50 mg) intramuscular.
3-Immunological reactions : due to presence of antibodies in donors blood that react with recipient cells

Acute reactions
-Anaphylactic shock mediated by donors IgA
-Allergic skin rash and rhinitis mediated by donors IgE
-Acute respiratory distress syndrome mediated by antibodies against recipient human leukocytic antigen

Delayed reaction
-If recipient is immunosuppressed donors T lymphocytes attacks recipient cells causing diarrhea, hypotension , fever
-On repeated transfusion : recipient produces antibodies against donor s platelets leading to hemorrhage

 

centrifugation .It is stored in concentration of 5% in 50% glucose solution at 4 0C.
2-Dried plasma: separated from liquid plasma by lyophilization (dry freezing) . It is stored dried in 40C and dissolved before use in half normal saline +2.5 % glucose. The dose is 10 ml /kg
3-Fresh Frozen plasma: prepared by freezing fresh liquid plasma at
-150C. It is the only plasma preparation that preserve clotting factors .It is solubilized in warm water bath and administrated in a dose of 10-20 ml/kg IV in hemorrhagic diseases
4-Synthetic plasma: solution containing the same ion concentration of human plasma used in gene therapy & fixation of bone metal implants
Indications
I-Replacement therapy
1-The first line treatment of burns
2-As an alternative for whole blood transfusion if not available .It keeps osmotic pressure but has very little oxygen carriage
Advantages : It is storage for long times ( months or years)
-It keeps osmotic pressure of blood and retain in circulation for long time
-It does not need cross matching if transfused in small amounts.
-Immunological and febrile reactions are rare
Disadvantages :-They have very limited oxygen carrying capacity
-It may transmit infections
-Overdose may cause heart failure
II-Exchange therapy(plasmaphoresis):
Removal of patient plasma which contain harmful autoimmune antibodies and replacing it normal plasma. It is two types:
Autologous: patient plasma is withdrawn , treated and re-injected
Homologous patient plasma is withdrawn and replaced by donor one.

Plasma constituents
1-Human serum albumen is used to
1-As blood or plasma substitute in hypovolemic shock
2-In cases of hypoalbumemia as a result of
Decrease synthesis in malnutrition ,starvation , mal-absorption or liver diseases
Excessive loss in urine in nephrotic syndrome
Excessive loss by skin in burns
Severe abdominal inflammation eg peritonitis , pancreatitis
Dose : 500 ml of 5% or 200 ml of 25 % solution slowly by IV drip.
2-Human gamma globulins : They protect against infectious diseases by provision of antibodies .They have two types:
Immunoglobulins :It contains non committed antibodies .
Hyperimmune gamma globulins : it is prepared from the plasma of donors with high titers of antibodies against a specific organism. Hepatitis B , tetanus toxin, herpes zoster, hepatitis A, or cytomegalovirus They are used to prevent infections in susceptible persons or during epidemics.
Human fibrinogen :It is used in bleeding disorders eg hypofibrinogenemia and disseminated intravascular thrombosis.
Human factor VIII is used for hemophila
Fibrin glue :consists of fibrinogen + bovine thrombin .It is used in lacerated wounds