Von Willebrand Flashcards
A 52-year-old woman is in the operating theatre.
She is having an operation to remove her gallbladder (cholecystectomy).
The surgeon notes that the wound is oozing a lot of blood and he is having to use the diathermy frequently to control the bleeding.
He decides to leave a drain in place as there is still a lot of blood pooling as they are closing the wound.
The surgeon asks the medical student to check again the blood results. She looks at the computer and replies that results are normal.
The surgeon asks the lab to do additional coagulation tests. 20 mins later the lab rings to say that aPTT and PT are both normal.
What could cause excessive bleeding?
What are your differentials?
Excessive bleeding during surgery, as described in the scenario, can be concerning and may have various underlying causes. Given that the surgeon has ruled out abnormalities in the standard coagulation tests, such as aPTT and PT, several other factors may be contributing to the bleeding. Here are some possible differentials to consider:
Platelet Dysfunction: Normal aPTT and PT results suggest that the patient’s coagulation factors and clotting cascade are functioning correctly. However, platelet dysfunction or low platelet count (thrombocytopenia) could lead to bleeding issues. A specific platelet function test, such as a bleeding time test or platelet aggregation studies, might be needed to evaluate platelet function.
Medications: Certain medications, such as anticoagulants (e.g., aspirin, warfarin), antiplatelet drugs (e.g., clopidogrel), or newer anticoagulants (e.g., dabigatran, rivaroxaban), can interfere with normal clot formation. It’s essential to review the patient’s medication history and discontinue any medications that may affect clotting prior to surgery.
Von Willebrand Disease: Von Willebrand disease, a bleeding disorder that affects the von Willebrand factor and platelet function, might not always be detected by standard coagulation tests. Specific von Willebrand factor assays may be necessary for diagnosis.
Coagulation Factor Deficiency: While aPTT and PT are normal, other specific coagulation factor assays (e.g., factor VIII, IX) could reveal deficiencies in specific clotting factors that standard tests do not detect. In the case of factor deficiencies, clotting is affected in a specific and often predictable manner.
Liver Disease: Severe liver dysfunction can impact the synthesis of clotting factors, including factors not typically assessed in routine coagulation tests. Assessing liver function and coagulation factor levels may be necessary to rule out liver-related coagulopathy.
Hemodilution: Excessive administration of intravenous fluids or blood products during surgery can lead to hemodilution, which reduces the concentration of clotting factors in the blood. This might result in bleeding complications. The use of fresh frozen plasma (FFP) or clotting factor concentrates can correct this.
explain a scenario where the patient’s clotting factor levels are assessed, and some abnormalities are found
The information you’ve provided suggests a scenario where the patient’s clotting factor levels are assessed, and some abnormalities are found. Specifically:
Factor VIII: Slightly decreased levels of factor VIII are observed. This can be indicative of Hemophilia A, which is characterized by a deficiency of factor VIII.
Factor IX: Factor IX levels are found to be within the average or normal range. This suggests that Hemophilia B (Factor IX deficiency) is not the cause of the bleeding, as factor IX levels are normal.
von Willebrand Factor (vWF): The level of von Willebrand factor is reduced. This is significant because von Willebrand factor plays a crucial role in platelet adhesion and blood clotting. Reduced vWF can lead to bleeding issues, especially when combined with a mild factor VIII deficiency.
Given these findings, the patient’s clinical presentation may align with a diagnosis of von Willebrand disease (vWD). von Willebrand disease is a bleeding disorder characterized by reduced or dysfunctional von Willebrand factor, which affects platelet function and can lead to bleeding issues similar to those seen in Hemophilia A (Factor VIII deficiency).
von Willebrand disease is a heterogeneous condition with varying subtypes and clinical presentations. Specific diagnostic tests, such as von Willebrand factor assays, are often used to differentiate between the different types of vWD and determine the severity of the condition.
The patient’s reduced von Willebrand factor levels, in combination with the slightly decreased factor VIII levels, could be indicative of a von Willebrand disease diagnosis. However, a thorough evaluation by a hematologist and further diagnostic tests are needed to confirm the specific subtype and establish an accurate diagnosis.
explain von Willebrand disease (VWD)
VWD is indeed a genetic disorder caused by missing or defective von Willebrand factor (VWF), which is a clotting protein. VWF has two critical roles in the blood clotting process:
Binding Factor VIII: VWF serves as a carrier protein for factor VIII. This binding stabilizes factor VIII and extends its presence in the bloodstream. Factor VIII is essential for blood clotting, and VWF helps maintain its function by preventing its rapid breakdown.
Assisting Activated Platelet Aggregation: VWF plays a crucial role in platelet adhesion and aggregation. When blood vessels are injured, VWF helps platelets stick to the damaged site and clump together, forming a platelet plug that’s the initial step in clot formation.
VWD is typically inherited in an autosomal dominant manner, meaning that the faulty gene responsible for the condition is located on chromosome 12 and can affect both men and women equally. However, the severity and symptoms of VWD can vary widely among individuals. Some may have a milder form of the disease, while others may experience more significant bleeding symptoms.
give an overview of the steps involved in the initial response to vessel injury and the formation of a platelet plug during hemostasis
Vessel Injury: When a blood vessel is injured or damaged, the initial response is vasoconstriction, which helps reduce blood flow at the site of injury.
Endothelial Lining Disruption: The endothelial lining of the blood vessel is disrupted due to the injury, exposing the underlying connective tissue, typically collagen.
Collagen Exposure: The exposed collagen in the vessel wall is a critical trigger for the next steps in hemostasis.
Platelet Adhesion: Platelets, which are small cell fragments in the blood, adhere to the exposed collagen at the site of injury. This adhesion is mediated in part by molecules like von Willebrand factor.
Platelet Activation: Upon adhering to the injured vessel wall, platelets become activated. This activation involves changes in their shape and the release of granules containing various substances, including clotting factors and chemical signals.
Platelet Aggregation: Activated platelets recruit and bind to each other, forming aggregates. This aggregation is essential for strengthening the plug and sealing the wound.
Platelet Plug Formation: The accumulation of platelets at the injury site creates a temporary seal, called a platelet plug. This plug helps prevent further blood loss and is the initial step in hemostasis.
explain the key points about von Willebrand disease (vWD)
Prevalence: Von Willebrand disease is estimated to affect about 1% of the general population, which corresponds to approximately 1000 per 100,000 people.
Variable Severity: Von Willebrand disease can vary in its severity, from mild cases that often go unnoticed to more moderate or severe forms.
Clinical Presentation: Individuals with von Willebrand disease may experience spontaneous bleeding from mucous membranes, such as nosebleeds and gum bleeding. They can also bleed excessively from wounds and may have menorrhagia (excessive menstrual bleeding).
Types of von Willebrand Disease:
Type 1: This is the most common type, accounting for about 70% of cases. It is characterized by quantitative defects, meaning that there is a decrease in the quantity of von Willebrand factor (vWF) in the blood. Type 1 is typically associated with mild disease.
Type 2: Type 2 von Willebrand disease accounts for about 25% of cases. It is characterized by qualitative defects in vWF. It is often inherited in an autosomal dominant manner and can range from mild to moderate in terms of disease severity.
Type 3: Type 3 von Willebrand disease is the most severe form, affecting about 5% of cases. It is inherited in an autosomal recessive manner and is characterized by a complete absence or virtually undetectable levels of vWF. Individuals with Type 3 von Willebrand disease have a high risk of severe bleeding episodes.
explain von Willebrand disease (vWD) and its impact on primary and secondary hemostasis
Von Willebrand disease is indeed a bleeding disorder that primarily involves defects in platelet function, specifically in platelet adhesion. As you mentioned, von Willebrand factor (vWF) plays a crucial role in hemostasis. It stabilizes factor VIII in the bloodstream, preventing its rapid degradation and extending its half-life. Additionally, vWF facilitates the adhesion of platelets to exposed collagen at the site of vascular injury, which is a key step in primary hemostasis.
Impact on Factor VIII: Abnormalities in vWF can lead to lower levels of factor VIII in the blood because vWF helps protect and maintain the stability of factor VIII. Consequently, individuals with von Willebrand disease can experience low factor VIII levels as a result of their underlying condition.
No Bleeding Into Joints: Unlike hemophilia (both Hemophilia A and Hemophilia B), individuals with von Willebrand disease typically do not experience bleeding into joints (hemarthrosis). This is because the primary issue in von Willebrand disease is related to platelet adhesion, not solely a clotting factor deficiency.
Treatment: The treatment of von Willebrand disease often involves the administration of desmopressin (DDAVP), which can stimulate the release of stored vWF and factor VIII from endothelial cells, temporarily increasing their levels in the bloodstream. In cases where desmopressin is not effective or contraindicated, infusions containing factor VIII and vWF concentrates can be used to manage bleeding episodes.
