About the Condition

Description/definition:

Valve hemolysis occurs when red blood cells (RBCs) are mechanically fragmented as they pass through a prosthetic heart valve with a paravalvular leak or far less commonly through a stenotic native valve.

Hemolytic anemia is anemia caused by premature destruction of red blood cells as defined by:

Otherwise unexplained anemia.
Signs of accelerated RBC production in the bone marrow (e.g., high reticulocyte count).
Signs of RBC destruction (e.g., elevated unconjugated bilirubin, lactate dehydrogenase [LDH], low haptoglobin).

Sub-clinical hemolysis is used to describe patients who meet the last two criteria but do not have anemia. In these patients, the bone marrow adequately compensates for the hemolysis, maintaining a normal hemoglobin.

The incidence of hemolysis in patients with cardiac prostheses varies widely according to the device type and its indwelling time.

Valve	Subclinical hemolysis	Hemolytic anemia	Comments
Native valve	Rare	Rare	Stenotic aortic > mitral valve
Surgical valve
Old generation mechanical valves, e.g., caged-ball prostheses	23-92%	up to 15%	Mitral valve > aortic valve; Diagnosis several years after implantation
Modern mechanical valve designs.	18% to 51%	<1%	Hemolytic anemia is an infrequent finding in absence of prosthesis malfunction.
Tissue valves	5% to 10%	<1%	Less common than with prosthetic valves
Transcath valve replacement
TAVR	15%-30%	Rare	Occurs within months of implantation; degree of patient-prosthesis mismatch.
TMVR	Scant data	Scant data
Valve repair	Rare	Rare	Most patients present with signs of hemolysis within 3 months from the operation.

Transcath, transcatheter; TAVR, transcatheter aortic valve replacement; TMVR, transcatheter mitral valve replacement

Pathophysiology:

Mechanical damage to the red blood cells (RBCs) due to increased shear stress as the cells pass through an abnormal channel created by:

Structural deterioration of valve, for example severe native aortic stenosis.
Paravalvular leak (most common cause)
- Turbulent flow through the valve or between the sewing ring and the native ring (incomplete apposition of the prosthetic sewing ring and the native annulus).
- May result from suture dehiscence due to:
  - Heavy annular calcifications
  - Endocarditis
  - Suboptimal surgical technique
  - Tissue friability

Valve type	Mechanism
Native valve	High blood flow velocity through a stenotic valve (especially aortic)
Surgical valve	PVL (most common), SVD, PPM, endocarditis, leaflet thrombosis
TAVR	PVL, PPM, increased red cell shear stress in the sinuses due to residual native valve fissuring and balloon‐induced endothelial denudation
TMVR	PVL due to incomplete sealing, device undersizing, or progressive left ventricular remodeling
Valve repair	Ring dehiscence, residual eccentric or para‐ring regurgitation, protrusion of suture material, free‐floating chordae in hyperdynamic left ventricle

LV; left ventricle; PVL, paravalvular leak; PPM; patient-prosthesis mismatch (refers to a prosthetic heart valve that is too small for size of patient); SVD, structural heart deterioration; TAVR, transcatheter aortic valve replacement; TMVR, transcatheter mitral valve replacement

Note: Hemolytic anemia causes an increase in cardiac output, which, in turn, worsens the rate of hemolysis, thus creating a vicious circle.

Diagnosis:

Consider the diagnosis of valve hemolysis in a patient with:

Cardiac prosthesis and unexplained anemia.
Positive screen for hemolysis:
- Elevated:
  - Reticulocytes
  - Serum:
    - LDH
    - AST
    - Bilirubin
- Decreased serum haptoglobin
Presence of schistocytes on peripheral smear.
Symptoms of congestive heart failure (also caused by prosthetic valve dysfunction).

Confirm diagnosis:

Confirmation may be challenging because there is no specific test for valve hemolysis.
Demonstration of paravalvular leak using either one of the following:
- Transthoracic echocardiography (TTE) – often identifies the site and mechanism of prosthesis dysfunction
- Transesophageal echocardiography (TEE):
  - Usually necessary
  - Mandatory if peri-mitral leak is suspected
- Degree of hemolysis is not necessarily proportional to the amount of regurgitation; other factors include:
  - Irregularity of the leaking site
  - Colliding angle

Other labs

Mean cell volume may be increased owing to presence of increased reticulocytes.
Red cell distribution width (RDW) may be increased owing to presence of increased reticulocytes.
Plasma free hemoglobin concentration may be increased.
Urine may show hemoglobinuria and/or hemosidinuria.

Treatment:

Management depends on the nature and location of the leak, the clinical condition of the patient, and the available expertise of the heart team responsible for the patient.

Medical therapy

Mild, compensated, hemolysis can often be managed by observation alone.
Blood transfusion as needed; risks include:
- Transfusion reactions
- Antibody formation
- Iron overload
Folic acid – prophylactic oral folic acid supplementation is recommended to prevent folate deficiency.
Iron supplementation – if necessary (iron is lost in the urine).
Beta blocker – can reduce shear forces in patients with paravalvular leak (PVL)‐related hemolysis reducing blood pressure and heart rate.
Pentoxifylline – improves blood viscosity and erythrocyte deformability.
Erythropoietin:
- Has been studied in several small series.
- Shown to be effective in reducing blood transfusion rate, especially if there is concomitant renal dysfunction.

Invasive therapy

For patients with severe symptomatic hemolysis despite maximal medical therapy.
Paravalvular leak repair:
- Transcatheter paravalvular leak (PVL) repair
- Open surgical PVL correction:
  - Has been shown to be a more effective method in treating severe hemolysis than percutaneous repair
  - Recommended by clinical practice guidelines for operable patients with mechanical prosthetic heart valve and intractable hemolysis or heart failure due to severe prosthetic or paraprosthetic regurgitation

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