Heyde Syndrome - An Overview

What Is Heyde Syndrome?

Heyde syndrome is a severe disease that mainly includes three conditions:

1. Aortic stenosis (AS).

2. Gastrointestinal bleeding.

3. Von Willebrand syndrome.

What Are the Factors Responsible for Causing Heyde Syndrome?

1. Von Willebrand Syndrome:

The main factor responsible for causing Heyde Syndrome is the acquired von Willebrand factor (vWF). Acquired von Willebrand syndrome contains a comprehensive category of syndromes, that are caused by the following activities:

• Proteolysis, it is the breakdown of proteins into smaller polypeptides or amino acids.

• Unusual binding of von Willebrand syndrome to tumor cells.

• Reduced synthesis of von Willebrand factor.

Von Willebrand factor is a glycoprotein that gets synthesized in megakaryocytes and endothelial cells. This factor plays a vital role in hemostasis (normal blood clotting in response to an injury), with the help of the platelet adhesion mechanism in which platelets get attached to the surface of sub endothelium and stabilizing factor VIII (plasma glycoprotein involved in blood coagulation). The characteristic feature of Heyde’s syndrome is the loss of multimers of the von Willebrand factor. When the von Willebrand factor passes through the stenotic aortic valve, there will be structural changes in the factor induced by the shear force and thus the aortic valve becomes more sensitive to the action of von Willebrand protease. This leads to the proteolysis of multimers of the von Willebrand factor (multimers are high molecular proteins) followed by the loss of platelets that induce hemostasis (acquired von Willebrand syndrome vWS).

2. Aortic Stenosis (AS):

The pathophysiology referring to shear forces is seen in the following other conditions:

• Hypertrophic cardiomyopathy.

• Left ventricular assist device placement (LVAD).

• Mitral regurgitation.

• Extracorporeal life support.

The patients having severe aortic stenosis most commonly suffer from acquired von Willebrand syndrome. There is a reduction in high molecular weight von Willebrand factor multimers in around 68 to 79 % of the cases. This loss of von Willebrand factor multimers leads to increased angiogenesis (the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis).

3. Gastrointestinal Bleeding:

The loss of von Willebrand factor multimers causes increased angiogenesis that is responsible for bleeding from angiodysplasia (swollen and fragile blood vessels) through an increase in angiogenesis with acquired von Willebrand syndrome.

What Are the Signs And Symptoms of Heyde Syndrome?

Gastrointestinal Bleeding:

1. Hematemesis (vomiting of the blood).

2. Hematochezia (passage of fresh blood in the stools).

3. Melena (presence of partly digested blood in the faeces).

4. Pain in the abdomen.

5. Pallor (paleness or loss of color from the skin or mucous membrane).

6. Presence of blood on rectal examination.

7. Orthostasis (a form of low blood pressure that occurs when standing up from sitting or lying down)

Aortic Stenosis:

1. Dyspnea on exertion (difficulty in breathing).

2. Syncope (fainting or sudden loss of consciousness).

3. Fatigue.

4. Chest pain on exertion.

5. Low volume and slow rising carotid pulse.

6. Ejection systolic murmur.

7. Absence of physiologic S2 split.

Acquired von Willebrand Syndrome:

1. Easy bruisability.

2. Mucosal bleeding.

3. Heavy menstrual bleeding.

4. Hemarthrosis (state of articular bleeding, that is, bleeding into the joints).

5. Hematoma (collection of blood outside the blood vessels)

How to Diagnose Heyde Syndrome?

1. Laboratory Tests: These include

1. Complete blood count(CBC): It is done to check for the count of platelets.

2. Coagulation tests such as a prothrombin time (PT) and activated partial thromboplastin time (aPTT): Increased aPTT (activated partial thromboplastin time) is related to the presence of acquired von Willebrand syndrome.

3. Test for faecal occult blood.

2. Von Willebrand Factor Assay:

The sensitive test for acquired von Willebrand syndrome is by checking the decreased levels of large high molecular weight multimers of von Willebrand factor by gel electrophoresis. But this method is not most commonly used as it takes too much time (around seven to ten days) and is expensive.

3. Platelet Function Assay:

For platelet function assay, the screening test is used to check primary hemostasis. Von Willebrand factor antigen and ristocetin cofactor (measures platelet aggregation) activities are usual. Platelet function assay is usually taken up as an initial screening test for acquired von Willebrand syndrome because it is achieved in a short duration.

How Does Heyde Syndrome Get Managed?

Management of Heyde syndrome is a multi-team approach that includes: a cardiologist, gastroenterologist, and primary care physician.

Heyde syndrome is managed by:

1. Managing gastrointestinal (GI) bleeding.

2. Repairing the aortic valve.

Management of Gastrointestinal Bleeding:

• Intravenous fluids and blood transfusion should be initiated for hemodynamic stability.

• Endoscopic interventions are to be used to track down the source of bleeding.

• Surgical and transcatheter-based aortic valve replacement is the traditional treatment for GI bleeding.

• Angiodysplasia is considered the most common cause of lower gastrointestinal bleeding. In cases of gastrointestinal bleeding caused by small bowel angiodysplasia, conventional techniques of upper and lower GI endoscopy are not used but the deep enteroscopy method is taken into consideration.

• CT Angiography is specified in cases of active bleeding pursued by angiography and embolization prior to localization.

• Surgical resection or intraoperative enteroscopy is rarely performed in cases of life-threatening bleeding but active cases of bleeding in angiodysplasia recognized during endoscopy need to be treated.

• The most commonly used non-contact technique is argon plasma coagulation (APC). This technique uses energy released from the ionized form of argon.

• Bipolar cauterization is another effective method used to lower the risk of perforation.

• Other methods used to manage gastrointestinal bleeding are mechanical hemostasis using endoscopic clips, injection sclerotherapy and radiofrequency ablation.

Repairing of the Aortic Valve

Two following methods treat aortic valve stenosis:

• Surgical Techniques such as bioprosthetic or mechanical methods: Bioprosthetic valves are most commonly used to prevent recurrent gastrointestinal bleeding.

• TAVR (Transcatheter Aortic Valve Replacement): This is the widely used treatment of choice in patients possessing a high risk for conventional surgical valve replacement. Transcatheter aortic valve replacement is a minimally invasive procedure where a new valve is inserted without removing the old, damaged valve.

What Is the Differential Diagnosis of Heyde Syndrome?

• Gastrointestinal hemorrhage such as peptic ulcer disease, diverticular disease, or gastrointestinal malignancy.

• Aortic valve disease such as isolated aortic stenosis/sclerosis, and aortic calcification.

• Disorders of hemostasis, such as hemophilia, VWF deficiency, thrombocytopenia, or clotting factor disorders.

Conclusion

Heyde’s syndrome is a complex multi-system disorder constituting a triad of gastrointestinal bleeding, aortic stenosis, and von Willebrand syndrome. It shows the clinical features of all the three conditions simultaneously, such as hematemesis, hematochezia, melena, syncope, fatigue, and dyspnea. The treatment mainly includes transcatheter aortic valve replacement.