Paroxsymal Cold Hemoglobinuria (PCH)

What is PCH?

        Autoantibody (Biphasic hemolysin) that binds to Red Blood Cells after the exposure to the Cold, and then the Red Blood Cells lyse and release Hemoglobin when body is warmed back up to body temperature.

Clinical Presentation:

         Recurrence of a fever and Dark urine 1-2 weeks after a Urinary Tract Infection (UTI)

         Can occur after the exposure to the Cold

         Hemolysis is usually acute and severe

              Hemoglobin < 5 g/dl

 

         Symptoms:

              Fever

              Abdominal Pain

              Hepatosplenomegaly (Enlarged Liver and Spleen)

              Fatigue

              Hemoglobinuria (dark urine; hemoglobin in the urine)

              Pallor

              Jaundice

 

Occurence:

    Occurs more often in children after viral infection but spontaneously resolves.

                Adults are more chronic, but not as severe

 

Diagnosis:

               Identification of symptoms and lab values

               Diagnostic Lab Test: Donath-Landsteiner Test

                            Patient plasma and Cells are incubated at Cold and Warm Temperatures.

                                             If Hemolysis appears in the tubes incubated first at 4C and then at 37C and not in the other tubes, it is Positive.

 

Antibody Specificity:

              The autoantibody is usually IgG with anti-P specificity and is a biphasic hemolysin.

 

Treatment:

             Supportive Therapy through blood transfusion and medications

ANTI-G

The G antigen is present on all RBCs that are D and/or C positive
            rare exception is the  rG cell
                       D and C negative but G positive

Why do we care about the G antigen and its antibody?
           When someone has anti-G it looks like they have antibodies to both D and C antigen
           Generally, you'd transfuse these patients with D negative and C negative blood which so happens to be G negative. So why do we care? If an obstetric patient has anti-G as opposed to anti-D + anti-C they do not have as severe Hemolytic Disease of the Newborn (HDN), but could make anti-D that would cause a severe form of HDN, so RhIg would be indicated.

       How do you know if it is anti-G or anti-D + anti-C?
                  Most reference labs will perform adsorption and elution studies to try to differentiate the two.
                        You'd utilize a D-C+G+ cell and incubate it with the patient's plasma. If anti-G is only present it will be removed from the plasma onto the cell, so when you elute the antibody you will find your eluate will react with both D+C- and D-C+ cells.
                                                 If it is anti-D + anti-C, your eluate will only react with the D-C+ cells.

Red Blood Cell Transfusion

Indications:
        Treatment of anemia in cases too severe to be treated by nutritional replacement or iron
        Loss of 10-15% of total blood volume during surgery
        Correction of perioperative anemia
        Hypotension associated with bleeding

The Transfusion Trigger:
           Generally is having a hemoglobin of 7 g/dl or less.
           If the patient has cardiac problems it is set at 10 g/dl

Why is having a low Hemoglobin and being anemic harmful?
           Hemoglobin transports Oxygen from the lungs to the tissues
           And transports Carbon dioxide from the tissues to the lungs
           Without enough hemoglobin the tissues do not get enough Oxygen and their is a build up of Carbon dioxide. This causes the tissues to become hypoxic and will begin to die. 

How does the body compensate for low hemoglobin levels?
         When hemoglobin levels get below 7 g/dl the heart starts to beat faster to pump blood through the body at a faster rate since their is less blood in the body.
                     This is why those patients with heart problems need to have a transfusion trigger that is higher (like 10 g/dl) because their heart cannot compensate.
          The tissues have a stronger affinity for Oxygen and will grab more of it as the Hemoglobin molecule passes by.

The risk of death from anemia is when the hemoglobin level reaches 3 g/dl. The body cannot compensate for the lack of oxygen and the body begins to shut down. Prolonged levels of a Hemoglobin of 3 or less usually results in death.

Red Blood Cell (RBCs) Transfusions:
        One unit of RBCs can increase the Hemoglobin by 1 g/dl and can be life saving in patients with severe anemia or bleeding.

What is a Type & Screen?

Do you know what testing is done on your blood when a doctor orders a type and screen?
     It is actually two tests:
          The Type:
              Determine your ABO and Rh type
                      Look for the A or B antigen on the Red Blood Cell and for anti-A or anti-B in the plasma
                                     This determines your ABO type
                     Look for the D antigen on the Red Blood Cell
                                     This determines if you are Rh positive or negative

         The Screen:
              Look for antibodies to Red Blood Cell antigens that have developed due to exposure to foreign Red Blood Cells through transfusion, pregnancy, or sharing of blood via needles.
              It is interpreted as either Positive or Negative
                      For Positive Antibody Screens, the antibody is identified and future blood transfusions should not have the Red Blood Cell antigen to the identified antibody.


What is meant by Type & Cross?
        This means that the doctor wants the lab to perform a Type & Screen, plus crossmatch Red Blood Cell untis for transfusion.

RhIg

What is RhIg?
      It a blood derivative that is used to prevent the formation of antibodies to the D antigen in Rh negative persons. Brand name is Rhogam.

Why is it important?
     Prior to the development of RhIg in the 1970s, fetal loss due to anti-D was as high as 46 in 100,000 pregnancies; now it causes 1.6 in 100,000. The D antigen is present in >85% of people and is highly immunogenic. The antibody that forms (anti-D) in a Rh negative person is IgG and can cross the placenta and destroy Rh positive fetal cells causing fetal anemia and/or death.

When is it administered?
    RhIg is given at to Rh negaitve pregnant women at 28 weeks gestation and within 72 hours after delivery.
    Or given to children or women of child-bearing age (< 50 years old) after receiveing Rh positive Red Blood Cells or Platelets.

Why is it administered?
    Since the D antigen is so immunogenic, as little as 2 ml of D positive blood can cause the formation of anti-D. There is the risk during pregnancy to have a fetal maternal bleed which would expose mom to fetal blood and develop this antibody, risks are highest after 28 weeks and at birth.

How does RhIg work?
    RhIg is an passive anti-D that binds to any D positive cells and those cells are then removed by the spleen. This prevents the person's body from recognizing it and making their own anti-D which lasts forever and may compromise future pregnancies. The RhIg generally is gone from the person's system in 3 months.

How much is given?
    One does is considered sufficient for the 28 week dose, but the risk of fetal bleed is greater during birth so another test, Fetal Maternal Hemorrhage Screen, must be performed to determine if more than one dose of RhIg is warranted.

Who is eligible to receive RhIg?
     Person must be Rh negative
     Person must not already have anti-D
     Must be exposed to Rh positive blood (from fetus or blood transfusion)

Are there other ways besides pregnancy and blood transfusion that one can develop Red Cell antibodies?
    Yes. There has been some evidence that sharing needles can expose persons to other peoples blood and potentially make antibodies.

Does RhIg prevent all cases of Fetal anemia due to antibody?
    No. There are many antigens on the Red Blood Cells and if antibodies to these are formed it can cause fetal anemia and/or death. Anti-D is just the most common one. There are no other products currently available to prevent these antibodies from forming.


Rhogam package insert

Medical Ethics Related to Blood Banking

Bioethics
  -  Moral conduct of the right and wrong in life and death issues.

Guidelines for confronting bioethical dilemmas.

                        Principle of Autonomy
                        People have the right to make decisions about their own life
            Principle of Beneficence
                        Do good
            Principle of Nonmaleficence
                        “First, Do no Harm”
            Justice
                        Treat everyone equally

Bioethical Issues
        Protecting human subjects in clinical trials
           Affordability
           Privacy
           Stem Cell Research
           Defending the United States against terrorism
           Organ and Tissue Procurement and allocation

Blood Bank related lawsuits on Bioethical Issues
          Transfusion Transmission of HIV/AIDS
          Informed Consent (Donor and Recipient)
          Untimely notification of positive test results
          Failure to offer Directed Donation services
          Failure of test performance

Other Ethical Issues about personal choice in healthcare
          Religion
               Jehovah's Witnesses generally refuse blood transfusion
          Euthanasia
          Fertility drugs and multiple births

Ethical Code of Conduct for Laboratory Professionals
     American Society of Clinical Laboratory Science (ASCLS) code of ethics

Prevention of Transfusion Transmitted Disease

A big concern with blood safety revolves around infectious disease transmission. Today, with our advances in testing the risk of acquiring HIV/AIDS from a blood transfusion is 1 in 2 million transfusions. Hepatitis C(HCV) is also a concern with a risk of 1 in 2 million transfusions. The biggest transfusion transmitted risk is bacterial transmission from Staphylococcus sp. with a risk of 1 in 500,000 in RBCs and 1 in 50,000 for platelets. Prevention of Transfusion Transmitted Disease is accomplished using a detailed Donor History Questionnaire (DHQ) and Infectious Disease Testing.

Infectious Disease Tesing is required on all transfused Blood products and they are the following:
     Hepatitis B surface Antigen (HBsAg)
     antibody to Hepatitis B core (anti-HBc)
     antibody to Hepatitis C (anti-HCV)
     Hepatitis C RNA (HCV RNA) - Nucleic acid testing (NAT)
     antibody to HIV-1/2 (anti-HIV-1/2)
     HIV-1 RNA (NAT)
     antibodies to HTLV-I/II (anti-HTLV-I/II)
     West Nile virus RNA (WNV RNA) (NAT)
      serologic test for syphilis

  Platelets are also tested for bacterial contamination

NAT is able to amplify and detect genetic sequences of a virus, so that those infected with these viruses are detected earlier (some within 10 days after exposure) to prevent transmission.