Bernard–Soulier syndrome

Bernard–Soulier syndrome (BSS), also called hemorrhagiparous thrombocytic dystrophy,^[1] is a rare autosomal recessive coagulopathy (bleeding disorder) that causes a deficiency of glycoprotein Ib (GpIb), the receptor for von Willebrand factor, which is important in clot formation.

The incidence is estimated to be less than 1 in 1 million persons, based on cases reported from Europe, North America, and Japan.^[2]

It is a Giant Platelet Syndrome that is characterized by abnormally large platelets.

Symptoms[edit source | editbeta]

As with other congenital platelet function defects, BSS often presents as a bleeding disorder with symptoms^[3] of:

• Perioperative and postoperative bleeding
• Bleeding gums
• Easy bruising
• Heavy menstrual periods
• Epistaxis
• Abnormally prolonged bleeding from small injuries

Characteristics[edit source | editbeta]

Characterized by prolonged bleeding time, thrombocytopenia, increased megakaryocytes (bone marrow platelet progenitors), and decreased platelet survival, Bernard–Soulier syndrome is associated with quantitative or qualitative defects of the platelet glycopotein complex GPIb/V/IX. The degree of thrombocytopenia may be estimated incorrectly, due to the possibility that when the platelet count is performed with automatic counters, giant platelets (which may be as frequent as 70–80% in occasional patients) may reach the size of red blood cells and, as a consequence, are not recognized as platelets by the counters. BSS platelets do not aggregate to ristocetin, and this defect is not corrected by the addition of normal plasma, distinguishing it from von Willebrand disease. The platelet responses to physiologic agonists is normal, with the exception of low concentrations of thrombin. Bleeding events, which may be very severe, can be controlled by platelet transfusion. Most heterozygotes, with few exceptions, do not have a bleeding diathesis.

It presents as a bleeding disorder due to the inability of platelets to bind and aggregate at sites of vascular endothelial injury.^[4]

HELLP syndrome

HELLP syndrome is a life-threatening obstetric complication usually considered to be a variant or complication of pre-eclampsia.^[1] Both conditions usually occur during the later stages of pregnancy, or sometimes after childbirth. "HELLP" is an abbreviation of the three main features of the syndrome:^[2]

• Hemolysis
• Elevated Liver enzymes
• Low Platelet count

Signs and symptoms[edit source | editbeta]

HELLP usually begins during the third trimester; rare cases have been reported as early as 21 weeks gestation. Often, a patient who develops HELLP syndrome has already been followed up for pregnancy-induced hypertension (gestational hypertension), or is suspected to develop pre-eclampsia (high blood pressure and proteinuria). Up to 8% of all cases present after delivery.

Women with HELLP syndrome often "do not look very sick."^[3] Early symptoms can include:

• In 90% of cases, either epigastric pain described as "heartburn" or right upper quadrant pain.^[3][4]
• In 90% of cases, malaise.^[4]
• In 50% of cases, nausea or vomiting.^[4]

There can be gradual but marked onset of headaches (30%), blurred vision, and paresthesia (tingling in the extremities). Edema may occur but its absence does not exclude HELLP syndrome. Arterial hypertension is a diagnostic requirement, but may be mild. Rupture of the liver capsule and a resultant hematoma may occur. If the patient has a seizure or coma, the condition has progressed into full-blowneclampsia.

Disseminated intravascular coagulation is also seen in about 20% of all women with HELLP syndrome,^[5] and in 84% when HELLP is complicated by acute renal failure.^[6] Pulmonary edema is found in 6% of all women with HELLP syndrome,^[5] and in 44% when HELLP is complicated by acute renal failure.^[6]

Patients who present with symptoms of HELLP can be misdiagnosed in the early stages, increasing the risk of liver failure and morbidity.^[7] Rarely, post caesarean patients may present in shock condition mimicking either pulmonary embolism or reactionary haemorrhage.

Pathophysiology[edit source | editbeta]

The exact cause of HELLP is unknown, but general activation of the coagulation cascade is considered the main underlying problem. Fibrin forms crosslinked networks in the small blood vessels. This leads to a microangiopathic hemolytic anemia: the mesh causes destruction of red blood cells as if they were being forced through a strainer. Additionally, platelets are consumed. As the liver appears to be the main site of this process, downstream liver cells suffer ischemia, leading to periportal necrosis. Other organs can be similarly affected. HELLP syndrome leads to a variant form of disseminated intravascular coagulation (DIC), leading to paradoxical bleeding, which can make emergency surgery a challenge.

An association has been demonstrated between long chain 3-hydroxyacyl-CoA-dehydrogenase (LCHAD) deficiency and maternal HELLP and AFLP (acute fatty liver of pregnancy). This inherited, autosomal recessive abnormality of fatty-acid oxidation can result in significant morbidity and mortality in infants, if untreated. Treatment with dietary manipulation is possible. Approximately 80% of infants with LCHADhave been born after pregnancies complicated by AFLP or HELLP. However, what is not known is how many pregnancies complicated by AFLP or HELLP result in infants with LCHAD deficiency.^[8]