Complications of donor and patient apheresis

 

Complication rates of donors:
Overall rate ranges between 0.81 to 2%
complication rate requiring hospitalization 1/200,000
this is in comparison to between 10 to 20% in whole blood donors.

Common reactions: hematoma, pain, citrate toxicity, vasovagal, vasovagal with syncope

 

Complication rate of therapeutic apheresis (for patients)
reported to be approximately 4.75%
reactions include: allergic febrile transfusion reactions, citrate toxicity, hypotension, vasovagal
mortality rate in therapeutic apheresis estimated to be 3 per 10,000 procedures

Citrate toxicity: a calcium chelator that inhibits coagulation. Normally citrate is distributed throughout the entire extracellular fluid it is rapidly metabolized and any calcium deficit is mobilized from albumin. Secondarily parathyroid mobilizes bone stores and renal handling of calcium increases urinary calcium resorption. Despite these companies employ mechanisms it is still possible to to see clinically significant hypocalcemia. Factors that have been associated with citrate toxicity are hypoventilation, hypoalbuminemia, total amount of citrate and the rate of infusion (high rate intermittent).

**Citrate toxicity cannot cause bleeding from inhibiting coagulation factors. This is because in order to prevent coagulation calcium levels must be reduced to 0.2 mmol per liter. This level of hypocalcemia is incompatible with life and occurs only in the machine and not in the patient.

Remember that between 40 to 55% of total calcium is albumin bound. Transfusing albumin is normally stripped of calcium and can cause a significant decrease in calcium store. It is recommended to add calcium gluconate to albumin prior to administration. You can also give intravenous calcium gluconate or slow the rate of infusion.

Keep in mind citrate also chelates magnesium. Clinical signs of hypomagnesiumemia include muscle spasm weakness decreased vascular tone and cardiac contractility abnormality. Important to remember that hypomagnesemia inhibits parathyroid hormone action and can be a secondary cause of hypocalcemia in addition to citrate toxicity.

Citrate is metabolized into bicarbonate. In settings where the patient cannot excrete bicarbonate significant metabolic alkalosis with resultant hypokalemia has been observed. Therefore remember to check your potassium before initiating therapy and replete as necessary.

 

ALLERGIC and ANAPHYLACTOID
urticaria and other allergic reactions that are seen in blood donors typically are an allergy to ethylene oxide. Ethylene oxide is used to sterilize the disposables. The combined plasma proteins and initiate an immune response. This is seen in donors of multiple donations.

Anaphylactic reactions may be triggered by ethylene oxide, hydroxyethyl starch, immunoglobulin A, albumin.

Immunoglobulin A deficiency is seen in one in 700 Caucasian. Must use IgA deficient blood products.

Anaphylaxis isnormally triggered by complement fragments C3a C5a as well as anti-bodies to immunoglobulin G & E.

ACE inhibitors:
electrostatic materials in the apheresis columns as well as enzymatic activity in donor albumin convert bradykininogen to bradykinin. Furthermore ace inhibitors in addition to blocking angiotensin-converting enzyme also block kninases (degradation enzymes of bradykinin). This leads to unopposed bradykinin activity which clinically presents flushing hypotension bradycardia dyspnea. That's why you want to stop all ace inhibitor therapy between one and two days prior to the procedure. If that didn't happen and you are suspecting this, immediately discontinue the procedure.

THROMBOCYTOPENIA OF PLASMA EXCHANGE
therapeutic plasma exchange expect to see a reduction in platelets anywhere between 0 to 71%. In the hematopoetic stem cell collections anywhere between 24 and 54% has been reported.
Plasma exchange also reduces coagulation factors, so monitor go as as well as fibrinogen. This is especially important in hemostatic challenged patients.

Reversing heparin induced bleeding - protamine sulfate dose of 1 mg for every 100 units of heparin.

Transfusion medicine – clinical notes

Patient has an anaphylactic reaction to albumin? It is likely sodium caprylate which is an additive in the mixture.

Sequence of clinical presentation of symptomatic hypocalcemia:

#1 paresthesias

#2 shivering lightheadedness 

#3 twitching and tremors

#4 nausea and vomiting

#5 hypotension carpalpedal spasm tetany and seizure

hold Ace inhibitors 24 to 48 hours prior to apheresis especially with LDL apheresis

Human immunoglobulin M - half life 10 days in the serum is highly efficient at fixing complement and agglutination.

Human immunoglobulin A- serum half-life is 5-8 interesting is a monomer in the serum but it is a dimer in secretions

there are two subclasses of immunoglobulin A IgA1 and IgA2, if you're suspecting an anaphylactic reaction to a blood transfusion in somebody who is IgA deficient is best to check in anti-IGA level and not the absolute IGA level because you can be deficient in one particular subclass and therefore the anaphylactic reaction is directed against a particular subclass which is deficient. Bottom line is draw the anti-IgA.

anti human globulin -this is a probably specific anti-immunoglobulin G and an anti-complement used for ABO blood typing

P antigen is the receptor for parvovirus can give you a paroxysmal cold hemoglobinuria that fixes complement upon rewarming than causing hemolysis

But blood cell antigen Kidd fixes complement and can cause intravascular hemolysis, exposure to this antigen in previous transfusions creates anti-bodies that are known to fade from circulation over time.

Clinically significant red blood cell antigens are of course the ABO groups, but also include Rh Kell Duffy Kidd and Ss.

Buffy is the receptor for plasmodium vivax

Donated platelets come in two particular flavors those that are acquired by apheresis and those that are whole blood derived.

This is important clinically because when you are transfusing platelets that are derived from apheresis you must match crossmatch the plasma because they are red blood cell depleted. However if you are transfusing platelets that are whole blood derived you must match ABO blood group because you have red blood cells present in the mixture. Even having small amounts of red blood cells present in the mixture is a risk because that creates allo sensitization to other clinically significant red blood cell antigens and thus increasing the risk of harmful reactions in future transfusions.

On the coagulopathy of trauma

massive injury rapidly consumes platelets. Fun facts: the surface area of capillaries in your lungs can cover a football field, you have enough platelets to cover 82 ft.² large amounts of tissue injury creates endothelial micro tears which expose collagen tissue factor and other platelet aggregating substances. This is seen clinically because in trauma 5% present with with platelet counts less than 100,000.

In the setting of major trauma coagulopathy is exacerbated by the presence of hypothermia and metabolic acidosis. These clinical factors create a feedforward cycle that worsens coagulopathy and thus inevitably results with high mortality. This is the coagulopathy of trauma

ACIDOSIS

For example the activity of Xa is reduced by 55% when the pH goes from 7.4 to 7.0 furthermore the activity of the prothrombinase complex has been found to be reduced by 70% at a pH of 7.0 compared to normal physiological pH. 

Mechanisms of action of platelet dysfunction in the setting of acidosis

the presence of H+ adversely affects Na/H exchange transport across the platelet membrane. The increased proton gradient inhibits the alkalinaztion of the platelet cytosol. An alkaline cytosol is necessary for platelet degranulation. If the platelet cytosol pH remains less than 7.0 then it cannot degranulate.

Thus one platelets and turn acidotic microcirculation they are very much impaired

An interesting pathophysiological idea is that acidosis inferred from systemic pH is falsely high in comparison to the microenvironment of low flow regions in trauma patients. The point being that you can correct serum pH but low flow tissue beds have a systemic acidosis that process as a result of low flow.

HYPOTHERMIA

Every 10°C decrease reduces enzymatic activities broadly by 50%. This includes coagulation reactions. An interesting idea is that prothrombin and activated partial thromboplastin time assays should be performed at the core temperature of the patient to get a true indicator of the degree of coagulopathy. Core temperature is below 33°C are significantly impaired.

DILUTIONAL COAGULOPATHY FROM LARGE VOLUME RESUSCITATION IN SEPSIS

current guidelines for volume resuscitation in sepsis do not adequately address clotting factor replacement during significant hemorrhage. 

Current protocol from Gonzales et al Journal of trauma in 2007 - if continued bleeding following six units of RBC transfusion than two units of FFP for every additional five units of RBC. No formal criteria on platelets or cryoprecipitate.

Borgman et al in Journal trauma 2007- found improved survival with a higher FFP to RBC ratio.

Additional miscellaneous gastrointestinal notes

clinical management of shortcut syndrome

#1 control the diarrhea – dihpenoxylate, opioids, anticholinergics

#2 controlled diet small frequent meals low in sugar (osmolarity)

#3 nutrient replacement specifically magnesium calcium and micronutrients #number four total parenteral nutrition

Alpha-1 anti-trypsin clearance - clinical marker for protein malabsorption

Painless outlet bleeding

#1 diverticulosis approximately 30%

#2 hemorrhoids 15 to 20%

#3 malignancy 15 and 20%

#4 colitis

Thiamine deficiency seen after bariatric surgery so-called bariatric beriberi

1 quart of caffeine can deplete your entire same in stores

hyperemesis gravidarum check thiamine, they can be deficient

Clinical history hopping differentiate radiation enteritis versus radiation proctitis

  -enteritis is bloody outlet bleeding, proctitis is hematochezia and pain

Chromium is a micronutrient cofactor necessary for the action of insulin. Therefore in patients with hyperglycemia consider that chromium may be deficient. This is especially true in the setting of total parenteral nutrition because many formulations are lacking this micronutrient.

Manganese access the setting of total parenteral nutrition can present as paper dense deposits in the basal ganglia

Post polypectomy bleeding window of presentation is normally between 5– 7 days

electrocautery causes delayed bleeding

Subtle clinical clues for picking up zinc deficiency -abnormal taste, acrodermatitis enteropathica

Copper deficiency can present in the setting up gastrectomy or chelator therapy

Mantle cell lymphoma often presents in a colon polyp

Solid tissue biopsy report says "granulocytic sarcoma" - that is an acute myeloid leukemia in the tissue

Diagnosing systemic lupus erythematosus

4/11 criteria
Serositis
oral ulcers oral ulcers
arthritis
photosensitivity
cytopenias autoimmune hemolytic anemia
renal failure, glomerulonephritis RBC casts
antiglare antibiotic titers double-stranded DNA titers, anti-Smith titers
immunologic phenomenon
neurologic phenomenon psychosis seizure
malar rash
discoid rash



Overheard in rounds "bursas don't do well when you put needles in them" meaning don't ever drain and inflamed bursa if you do they can be complicated by chronic nonhealing and drainage

Autoimmune polyglandular endocrine disorders specifically adrenal and thyroid- be very careful if you treat a thyroid disorder first you may cause cardiovascular collapse from adrenal insufficiency.


Anti-emetics

Compazine promethazine Thorazine - dopaminergic antagonism cholinergic antagonism is to monarchic antagonism, good to use in the setting of a small bowel obstruction because they are not pro-motility agents

Haloperidol – powerful dopaminergic antagonism with very little anticholinergic activity. Special mention because this is a medication that is great for renal failure because it is not clear by the kidney.

Metoclopramide - dopaminergic antagonism and at high doses serotonergic antagonism, this agent has promotility so avoided the setting of small bowel obstruction. Good to double cover in people with gastroparesis.

Antihistamines great antinausea if you're trying to double cover motion sickness or a vestibular component.

Anticholinergics – scopolamine, atropine. Okay to use in the setting of small bowel obstruction because they do not increase gastrointestinal motility

Cannabinoids -have been used for chemotherapy induced nausea and also helps with appetite stimulation, dysphoria in the elderly has been observed clinically

Ondansetron granisetron, alosetron -best pick for chemotherapy induced nausea

Corticosteroids -useful for nausea and also covering appetite stimulation as well as increased intracranial pressure, major con are the long-term side effects

Headache in the emergency department - clinical guidelines

the patient presents with headache of unknown etiology to the emergency department. After evaluating for red flag symptoms on the clinical history and deciding on any or all appropriate laboratory investigations and imaging the following is a general treatment guideline.

Gentle intravenous hydration and ketorolac 30 mg IV, intramuscular will last longer but some people prefer not to have a shot. It's also recommended to choose an anti emetic. Typically Compazine between 2.5 to 10 mg, metoclopramide between 5 to 10 mg or droperidol, up to 2.5 mg (it's a QT Prolonger see may want to get EKG).

Did it get better? If so safe to go home, consider dexamethasone 10 mg intravenous out the door, with outpatient follow-up

Not getting better? Consider whether the patient has any contraindications to ergot alkaloids (cardiovascular disease serotonergic agents or other vasoconstrictors onboard, history of myocardial infarction, pregnancy, hypertensive, hypersensitivity, history of basilar migraine etc.)

If no contraindications go ahead with 0.5 mg IV as a test dose.

  If the patient tolerates the ergot alkaloids go ahead and give another 0.5 mg IV up to an hour later

If there are no contraindications 1 g intravenous valproate over an hour.

If resolved safe to go home with follow up, consider given dexamethasone 10 mg intravenous out the door.

However is not getting better consider opioid. If there opioid naïve and they get better out the door with outpatient follow-up. If they are not opioid naïve or they are not getting better on an opioid consider a neurology consult.

Keep in mind:

valproate should be avoided in the setting of liver disease, hypersensitivity that's been documented or in the rare instance of urea cycle disorder.