POTD: Complications of Blood Transfusion

>> Hemolytic:

• Acute Intravascular Hemolytic Reaction

  • Overview:

    • Occurs when recipient's antibodies recognize and induce hemolysis of donor's RBCs

      • Most of the transfused cells are destroyed, which may result in activation of the coagulation system, DIC, and release of anaphylatoxins and other vasoactive amines

    • Caused by ABO incompatibility; usually the result of technical errors

    • Risk is 1 to 4 per million units transfused

    • Serum haptoglobin will be decreased, serum lactate dehydrogenase will be elevated, and direct antigen (Coombs) test usually will be positive

  • Signs/Symptoms: Fever, chills, low back pain, flushing, dyspnea, tachycardia, shock, hemoglobinuria

  • Management:

    • Immediately stop transfusion

    • IV hydration to maintain diuresis; diuretics may be necessary

    • Cardiorespiratory support as indicated

  • Evaluation:

    • Retype and repeat cross-match

    • Direct and indirect Coombs test

    • CBC, creatinine, prothrombin time, activated partial thromboplastin time

    • Haptoglobin, indirect bilirubin, lactate dehydrogenase, plasma free hemoglobin

    • Urine for hemoglobin

• Delayed Extravascular Hemolytic Reaction

  • Often have low-grade fever but may be entirely asymptomatic

  • Usually presents days to weeks after transfusion

  • More common than intravascular hemolytic reaction; rarely causes clinical instability

  • Hemolysis most commonly occurs in the spleen and occasionally in liver and bone marrow

  • Requires hemolytic workup as above to investigate the possibility of intravascular hemolysis

    • May be identified by a positive Coombs test, elevated unconjugated (indirect) bilirubin level, and less than expected increase in hemoglobin from the transfusion

>> Febrile:

• Overview:

  • Characterized by fever during or within a few hours of a blood transfusion

  • Quite common => occurs in approximately 1 per 300 units of PRBCs infused 

  • Most common in multiparous women or multiply transfused patients (pts who have been exposed to foreign blood antigens)

  • For patients with recurrent febrile reactions, use of leukocyte-reduced blood products may be helpful

• Signs/Symptoms: Fever, chills

• Management:

  • Stop transfusion

  • Initially manage as intravascular hemolytic reaction because one cannot reliably distinguish between the two

  • Can treat fever and chills with Acetaminophen

  • Consider infectious workup

• Evaluation:

  • Hemolytic workup as above

>> Allergic:

• Overview:

  • Caused by an immune response to transfused plasma proteins

  • Pts with immunoglobulin A deficiency may experience severe anaphylactic reactions due to presence of immunoglobulin A in donor products

    • Washing the plasma from the RBCs minimizes this type of reaction

• Signs/Symptoms: 

  • Mild: urticaria, pruritus

  • Severe: anaphylaxis => dyspnea, bronchospasm, hypotension, tachycardia, shock

• Management:

  • Stop transfusion

  • If mild, reaction can be treated with Diphenhydramine; if symptoms resolve, can resume transfusion

  • If severe, may require cardiopulmonary support; do not restart transfusion

• Evaluation:

  • For mild symptoms that resolve with Diphenhydramine, no further workup is necessary

  • For severe reaction, do hemolytic workup because initially may be indistinguishable from a hemolytic reaction

>> Infectious:

• HIV-1: 1 per 6 million units transfused

• HIV-2: Unknown, but extremely low

• Human T-cell Lymphotropic Virus Types 1 and 2: 1 per 640,000 units transfused

• Hepatitis B: 1 per 1 million units transfused

• Hepatitis C: 1 per 100 million units transfused

• Parvovirus B19: 1 per 10,000 units transfused

• Note: Blood is not tested routinely for CMV unless recipient is seronegative AND either pregnant, a potential or present transplant candidate, immunocompromised, or a premature infant

  • Leukocyte-reduced blood components further decrease the risk of CMV transmission to susceptible populations because most of the virus resides in leukocytes

>> Transfusion Related Acute Lung Injury:

• Thought to be due to granulocyte recruitment and degranulation within the lung

• Usually a complication of fresh frozen plasma or platelet transfusion; rare after PRBC transfusion alone

• Presents with respiratory distress and bilateral pulmonary infiltrates due to noncardiogenic pulmonary edema, during or within 6 hours of transfusion

• Often self-limiting and resolves spontaneously with supportive care

>> Other:

• Hypervolemia

  • Rapid volume expansion may occur leading to transfusion-associated cardiovascular overload

  • Pts with limited cardiovascular reserve (infants, severe chronic anemia, elderly) => highest risk

• Electrolyte Imbalance

  • Hypocalcemia, hypokalemia or hyperkalemia rarely occur

  • The anticoagulant citrate is a component of many blood preservatives and chelates calcium

    • Pts with normal hepatic function metabolize the citrate to bicarbonate

  • Rarely, hepatic metabolism is overwhelmed; hypocalcemia can develop and/or the excess bicarbonate generated causes alkalemia, driving potassium into cells and causing hypokalemia

  • Potassium content in stored blood products increases during storage; uncommonly, pts with renal insufficiency or neonates can develop hyperkalemia

POTD: Painless Visual Loss

>> CRAO/CRVO

• CRAO: Occlusion of the main artery that supplies the retina or its branches (BRAO); typically due to an embolus from proximal atherosclerotic disease

• CRVO: Occlusion of the main veins draining the retina; results in secondary hemorrhage and ischemia

Risk Factors: Older age, Vasculopathy

History:

• Sudden painless monocular vision loss or partial loss

• Can be transient, stuttering, or permanent

Exam:

• Classic fundoscopy findings of CRAO: pale retina with a cherry red spot over the macula as a result of ischemia and edema

• Classic fundoscopic finding of CRVO: blood and thunder

• Fundoscopic findings may be subtle in:

  • Pts who present early

  • Pts with intermittent symptoms

  • Pts with branched retinal artery occlusions (BRAO)

Management:

• Most therapies that have been studied are not very effective

• Eyeball massage and globe paracentesis are sometimes used for CRAO

• Intra-arterial tPA has also been used for CRAO

>> Retinal Detachment

Overview:

• May occur as a result of trauma, but the majority of cases are spontaneous

• Typically preceded by posterior vitreous detachment (PVD)

  • As the vitreous humor dehydrates and shrinks with age, it can detach from retina

  • The resulting traction on the retina then puts the pt at risk for retinal detachment 

• The symptoms of PVD are primarily floaters and flashers

• Most cases of PVD are self-limited

  • However, the risk of progression to retinal detachment is high in the days and weeks following the initial symptoms

• Can be difficult to distinguish PVD from early retinal detachment!

  • Unless symptoms are chronic and unchanging, consider retinal detachment when pts present acutely with flashers and floaters

Risk factors: Older age, Severe myopia (nearsightedness), Glaucoma, Cataract surgery, Diabetic retinopathy

History:

• Early warning sign is acute onset of flashers and floaters

• Curtains moving across visual field

• Visual field cuts

• Painless monocular vision loss

Exam:

• Visual acuity may be completely normal if early; it is important to test visual fields

• An advanced detachment can be seen with direct fundoscopy

Management:

• Macula on: vision is preserved; emergent surgery may halt progression and preserve vision

• Macula off (the macula has detached): severe vision loss in central visual field

• Presumed retinal detachment requires emergent Ophthalmologic evaluation to preserve the pt's vision!

>> Vitreous Hemorrhage

Risk factors: Diabetes, Hypertension, Vasculopathy

History:

• Sudden or staggered loss of monocular vision

• May present similarly to PVD or RD

• May also present as blurry vision

Exam:

• Decreased red reflex; may be difficult to see fundus

• Ultrasound is very effective at identifying blood in the vitreous!

Management: 

• Pts may follow up urgently in Ophthalmology clinic for treatment

• Return precautions for worsening symptoms/pain

• Anticoagulation is generally not discontinued

POTD: Painful Visual Loss

>> Acute Angle Closure Glaucoma

Presentation: 

• Extremely painful (deep, boring pain); frequently associated with vomiting

Exam:

• A red, angry appearing eye, firm to touch

• Cloudy “steamy” cornea

• Decreased visual acuity (may be profound)

• Markedly elevated IOP (generally > 40 mm Hg)

Management:

• Treat pain and give antiemetic

• Consult Ophthalmologist emergently

• Carbonic anhydrase inhibitors - Acetazolamide

• Topical beta blockers - Timolol

• Mannitol or Glycerol IV

• Alpha agonist drops - Apraclonidine

• Definitive therapy is surgical; involves laser iridectomy

>> Optic Neuritis

Causes: Multiple sclerosis (1/3 of patients with optic neuritis will develop MS), Other causes - idiopathic, infections (syphilis, measles, TB, crypto, etc), and autoimmune diseases

History:

• Painful monocular vision loss

• Pain behind eye and with eye movements 

Exam:

• Loss of central vision; peripheral vision is preserved

• Afferent pupillary defect (APD)

  • Anything that affects the optic nerve will cause an APD

  • Not specific to optic neuritis; may occur in any condition where light cannot reach the retina

• Red desaturation test

  • Take a dark red item and have the patient look at it covering one eye and then the other

  • Affected eye will see it as lighter red or pink

Management:

• Consultation with Ophthalmology and Neurology are both appropriate

• MR brain looking for plaques of MS

• Admit for IV steroids (Methylprednisolone); very high doses are used

>> Giant Cell Arteritis

History:

• Painful monocular vision loss

• May have headache, especially over the temporal areas

• Strong association with Polymyalgia Rheumatica (painful chronic condition in older patients causing fatigue and muscle pain)

• Jaw claudication (aching pain with chewing) is an important clue

Exam:

• Palpate and inspect area near temporal arteries for tenderness and nodularity

Management:

• Patients with any visual loss should be admitted for IV steroids

  • Methylprednisone 0.5-1 gm daily x 3 days (similar to optic neuritis or MS)

• If no vision loss, you can start Prednisone 1 mg/kg PO

• ESR should be draw; temporal artery biopsy should then be performed in the next week to confirm diagnosis