– This produces hypokalemia, hypomagnesemia and hypophosphatemia
– Additional fluid load administered can result in congestive cardiac failure, cardiac arrhythmias and sudden death
y Liver dysfunction, fatty infiltration and steatosis y Gallstones.
Gastrointestinal complications y Abdominal cramps y Abdominal distension
y Pneumatosis intestinalis and small bowel necrosis especially in the critically ill patients.
Tube related complications y Displacement
y Blockage y Perforation y Infection y Malposition.
2. Both the intrinsic and extrinsic pathways once activated by any of the above causative factors lead to activation of the clotting cascade which finally leads to increased intravascular coagulation and thrombosis
3. Thrombosis at a systemic level cause the following reactions:
Clinical features
y Oozing from all IV line sites y Petechiae and ecchymosis
y Gum bleeding, epistaxis, GI hemorrhage y Shock, renal failure
y Intracranial bleeding and pulmonary hemorrhage y Clinical features of underlying disease
Investigations y Thrombocytopenia y Prolonged PT and aPTT
y Decreased fibrinogen and factor 8 levels
y Increased fibrin degradation products and D-dimer levels y Fragmented RBCs on peripheral smear
Management
y Management of underlying cause y Volume resuscitation
Next line of therapies are used once underlying cause is corrected or in life threatening situations.
y Platelet transfusion to keep platelet >50,000/cu mm y Cryoprecipitate to keep fibrinogen level >100 mg/dL y FFP to replenish clotting factor and INR <1.5
y Indications of heparin therapy (to give always alongwith antithrombin 3 infusion) – Chronic DIC with no overt bleeding
– When cause is amniotic fluid embolus – When cause is promyelocytic disorders
y EACA—given in hyperfibrinolytic state. Five gram loading dose is followed by 1 g/hr to block the fibrinolytic response.
Results
Despite all therapeutic measures, DIC has increased mortality because of both the DIC part and the underlying disease part.
Q22. Write a note on Blood “substitutes”.
Ans. Fluids that carry oxygen
Ideal blood substitute has following features y Deliver oxygen
y No compatibility testing required y Prolonged shelf life
y Cost effective y Fewer side effects y Persist in circulation Classes
Biomimetic Abiotic
Also called hemoglobin oxygen carriers
(HbOC) Also called perfluorocarbons (PFC) or
nonhemoglobin oxygen carriers
(HbOC) – Three generations of HbOCs have been prepared but none have been approved for routine use by FDA.
Problems with first generation HbOC include:
y Osmotic diuretic effect y Renal toxicity
y Short half life
y Coagulation abnormalities
y Vasoconstrictive properties because of scavenging of nitric oxide by free Hb Second generation HbOC:
y They are pasteurized, compatibility testing free, long shelf and circulation life, no renal toxicity
y Include DCLHb (Diaspirin cross linked Hb) – made from outdated human blood Hb, polymerised bovine Hb – HbOC – 201 and Polyheme—removes almost all tetrameric Hb and therefore thought to be more efficacious as because it has increased molecular weight, it has increased intravascular time
y Problems include free radical generation and exacerbation of reperfusion injury, methemoglobin production, immunosuppression and enhanced endotoxin pathogenicity
y Polyheme is associated with increased risk of myocardial infarction and therefore not FDA approved.
Third generation HbOC y Liposomal HbOC y Microsphere HbOC
y These have oxygen dissociation curve similar to RBC y Still under research
PFCs (Abiotic)
Dissolve more oxygen than plasma and therefore thought to be useful as blood substitutes.
Problems
y Immiscible in water and therefore need to be delivered as microdroplets
y Oxygen dissociation curve is linear and not sigmoid and therefore high FiO2 is required y Need to be kept frozen.
Second generation PFCs
y Have increased oxygen carrying capacity y Can be stored at 4°C
y Addition of lecithin as emulsifier has eliminated the adverse effects due to complement activation
y For example, oxygen, oxyflour, oxycyte
y Problems include increased incidence of vasoactive events mainly stroke
y Conclusion on their studies so far say that “PFCs are not free of side effects and therefore not efficacious for oxygen delivery and use”
Q23. Enumerate the different blood components and write in brief about each of them.
Ans.
Whole banked blood y Upto 450 mL/donor
y Increase Hb by 1g/dl and hematocrit by 3 % per 1 bag whole blood
y Benefit is that it is metabolically more active and it is coagulation factor rich y Disadvantage is that volume overload can occur
Fresh whole blood
y When transfused within 24 hours, it has shown improved outcomes in trauma associated coagulopathy.
y Provides greater coagulation factors levels.
Packed RBCs (hematocrit is 60–70%)
y Prepared by removing supernatant plasma after centrifugation y Volume is 200–250 mL
y Preserved with using SAG-M (saline, adenine, glucose, mannitol) or CPDA (citrate, phosphate, dextrose, adenine), stored up to 35 days.
y Maximum half life of transfused RBC is 50 days (N – 120 days) Leucocyte reduced (filtration)/washed (saline) RBC
y This process decreases HLA alloimmunization, febrile nonhemolytic transfusion reaction, decreases mortality due to infections (CMV) and decreases refractoriness to platelet transfusion.
Fresh frozen plasma y Volume 200–250 mL y Stored at –30°C
y First line therapy in fluid resuscitation in trauma associated coagulopathy in damage control resuscitation
y No rhesus antigen limitation y Increases all factor levels by 2%
y Rich in fibrinogen (400 mg), protein C, protein S, antithrombin and plasma proteins.
Cryoprecipitate
y Supernatant of fibrinogen
y Rich in factor 8 (80 units) and fibrinogen y Volume 15–17 mL
y Store at –40 to –50°C Platelet concentrates y Volume 50 to 70 mL
y Stored with constant agitation up to 5 days at 24°C y Increases platelet by 5 to 10,000/unit
y Very useful for patients with bleeding disorders and in patients on clopidogrel therapy requiring surgery. It also require continuos infusion during procedure
y 6 random donor platelets = 1 apheresis platelet unit.
Prothrombin complex concentrates y Factor 2, 9 and 10.
y Used mainly to treat warfarin overdose Autologous blood
y Can be taken from patients planned for surgery with collection starting at around 40 days before surgery in patients with Hb> 11 g/dL and hematocrit >34%
y Collection is done at weekly interval with maximum 5 collections and last collection not less than 5 days before surgery.
Indications of blood transfusion
y Chronic anemia—in nonoperative patients who are not bleeding, Hb<6 g/dL is a definite indication. Exception—in cardiac patients, Hb< 8 g/dL is a definite indication
y In perioperative patients and in patients with bleeding, Hb<8 g/dL is an indication y In patients with acute blood loss >20% as a part of damage control resuscitation.
Q24. Enumerate the complications of blood transfusion and discuss their management in brief.
Ans.
y Incidence—10%
y Rate of infection transfer—HBV (30%) > HCV (3%) > HIV (0.3%) y Most common cause—human error
y Most common reaction—febrile nonhemolytic transfusion reactions (FNHTR)
y Most lethal—TRALI > ABO incompatibility (hemolytic disorder) > bacterial contamination of platelets
y Most lethal infection—hepatitis.
Classification of reactions that can occur even with single transfusion
Causes FNHTR
y A form of graft versus host disease to transfused blood (GVHD)
y Preformed cytokines in donated blood and antibodies to donated blood Infections
Viruses HCV, HBV, HGV, CMV
HIV, HTLV, west nile virus
Prion CJD (Creutzfeldt-Jokob disease)
Bacteria Gram negative (RBC)
Gram positive (Platelet)
Yersinia, Pseudomonas, Syphilis, Brucellosis.
Parasites Plasmodium, Babesia, Ehrlichia, Chagas disease
Allergy/anaphylaxis
y It is used for soluble transfusion of constituents TACO (Transfusion associated circulatory overload) y Large volume rapid transfusion
TRALI (Transfusion related acute lung injury)
y Anti—HLA antibodies or anti-HNA antibodies to pulmonary cells and leukocytes result in noncardiogenic pulmonary edema
y Onset is always within 6 hours.
Hemolytic
y Acute—preformed IgM to ABO antigen y Delayed—preformed IgG to non ABO antigen
Clinical presentation y Acute hemolytic reaction
In awake— most common symptom is pain along intravenous site > flushing > back and chest pain
most common sign is oliguria > hemoglobinuria In anesthetised—ongoing oozing and bleeding and hypotension y Delayed Hemolytic reaction
Indirect hyperbilirubinemia, anemia, elevated haptoglobin, positive Coomb’s test y Other symptoms—fever, chills, vomiting, diarrhea, rashes, itching, hives.
Complications due to massive transfusion y Hypocalcemia
y Iron overload y Hypothermia y Coagulopathy y Hypo/hyperkalemia y Thrombocytopenia y TACO
y Thrombophlebitis/Air embolism/DIC.
Q25. Write a note on plasmapheresis.
Ans. It is basically the removal, therapy and return/replacement of blood plasma into the blood circulation. This is also used as a method to collect plasma for industrial purpose. This is thus an extracorporeal therapy or segregation method.
Procedure
y Blood is initially taken out through a needle and plasma is removed by a cell separator which can be a discontinuos flow/ continuos flow centrifugation or plasma filtration y After plasma separation, the blood cells are returned back into circulation while the
plasma is treated to remove the antibodies or other disease producing substances and then returned into the circulation
y In plasma exchange therapy, the patient’s plasma is discarded and replaced with replacement donor plasma, albumin or saline with added proteins
y Plasmapheresis just removes the products that are harmful. The disease treatment requires immunosuppression or other treatment to decrease the production of the substance or antibody.
Applications As therapy
y Behcet’s syndrome
y Chronic demyelinating polyneuropathy y Guillain-Barre syndrome
y Refsum disease
y Myasthenia Gravis/Lambert-Eaton syndrome
y Thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome
y HELLP syndrome, HIV Related neuropathy y Antiphospholipid antibody syndrome and so on
y It is also used to reduce blood viscosity in diseases such as Waldenstrom macroglobulinemia, cyoglobulinemia, etc.
As segregation process
y Here the plasma donors are drained of blood similarly as in treatment and the plasma is separated from the blood and the donor red cells are returned back to circulation. This allows nearly up to 1 liter of plasma to be donated at a time and also frequent (weekly) donation
y The plasma can then be used as direct plasma transfusion or segregation into factors, albumin, immunoglobulin or fresh frozen plasma transfusion.
Complications
y Bleeding at the catheter site, infection, hematoma y Risk of transfusion reactions
y Citrate toxicity and hypocalcemia
y Immunosuppression and increased susceptibility to infections y Transfusion transmitted infectious diseases.