What are the similarities and differences between Type 2 von Willebrand's disease and Factor XI (11) deficiency?

Similarities and Differences Between Type 2 von Willebrand's Disease and Factor XI Deficiency

Type 2 von Willebrand's disease and Factor XI deficiency are both inherited bleeding disorders, but they differ significantly in their pathophysiology, clinical presentation, and management approaches.

Similarities

• Inheritance Pattern:

  • Both are inherited bleeding disorders that can affect males and females 1, 2

• Clinical Manifestations:

  • Both can cause mucocutaneous bleeding symptoms 1, 2
  • Both disorders may lead to excessive bleeding following surgery, dental extractions, or trauma 1, 2
  • Both can have variable bleeding tendencies between individuals, even with similar factor levels 2, 3

• Laboratory Diagnosis:

  • Both require specialized laboratory testing for accurate diagnosis 1, 2
  • Both may require repeated testing to ensure accurate diagnosis 4

• Treatment Options:

  • Both may be managed with factor replacement therapy for severe bleeding episodes or before invasive procedures 1, 2
  • Antifibrinolytic drugs may be beneficial in both conditions 5, 2

Differences

Pathophysiology

• Type 2 von Willebrand's Disease:

  • Qualitative defect in von Willebrand factor (VWF) function 1, 6
  • VWF is a multimeric plasma glycoprotein that mediates platelet adhesion and aggregation at sites of vascular injury 4
  • VWF also carries and stabilizes factor VIII in circulation 1, 4
  • Type 2 VWD has four subtypes (2A, 2B, 2M, 2N), each with distinct functional abnormalities 1, 6:
    • Type 2A: Decreased high-molecular-weight VWF multimers leading to defective platelet adhesion 6
    • Type 2B: Increased affinity for platelet glycoprotein Ib 6
    • Type 2M: Defective platelet adhesion despite normal multimer distribution 6
    • Type 2N: Decreased affinity for factor VIII 6

• Factor XI Deficiency:

  • Quantitative deficiency of factor XI, a component of the intrinsic coagulation pathway 2
  • Factor XI is activated by thrombin and plays a role in the revised model of blood coagulation 2
  • No subtypes based on functional abnormalities like in Type 2 VWD 2

Epidemiology

• Type 2 VWD:

  • Part of the most common inherited bleeding disorder (VWD affects up to 1% of the population) 1, 4
  • Type 2 accounts for most non-Type 1 VWD cases 1
  • No strong ethnic predilection 1

• Factor XI Deficiency:

  • Much less common than VWD in the general population 2
  • Particularly common in Ashkenazi Jews (higher prevalence) 1, 2
  • Two specific mutations account for most cases in Ashkenazi Jewish populations 2

Clinical Presentation

• Type 2 VWD:

  • Typically presents with mucocutaneous bleeding (epistaxis, easy bruising, oral cavity bleeding) 5
  • Heavy menstrual bleeding is common in women 1, 5
  • Intracranial hemorrhage is extremely rare 4
  • Severity correlates with the specific subtype and degree of VWF dysfunction 1, 6

• Factor XI Deficiency:

  • Generally milder bleeding tendency than hemophilia A or B 2
  • Bleeding typically provoked by surgery rather than spontaneous 2
  • Even severe deficiency often presents with only mild bleeding tendency 2
  • Approximately 48% of heterozygotes demonstrate a bleeding tendency 3
  • Bleeding risk not strictly correlated with factor XI levels 2, 3

Laboratory Diagnosis

• Type 2 VWD:

  • Diagnosis requires specialized assays of VWF function 5
  • Tests include VWF antigen, VWF activity (ristocetin cofactor), factor VIII levels, and VWF multimer analysis 1, 5
  • VWF is an acute phase reactant, so levels can fluctuate with stress or inflammation 4

• Factor XI Deficiency:

  • Diagnosed primarily by measuring factor XI activity levels 2
  • Prolonged activated partial thromboplastin time (aPTT) is typically seen 2
  • Prothrombin time (PT) is usually normal 2
  • Factor XI levels don't always correlate with bleeding tendency 2, 3

Treatment Approaches

• Type 2 VWD:

  • Desmopressin (DDAVP) may be effective for mild cases, particularly Type 2A 1, 5
  • VWF/FVIII concentrates are used for more severe cases or when DDAVP is ineffective 5, 7
  • Treatment targets both hemostatic functions of VWF: platelet adhesion and factor VIII stabilization 4, 7

• Factor XI Deficiency:

  • Fresh frozen plasma or factor XI concentrates for severe deficiency 2
  • Factor XI concentrate use in older patients has been associated with thrombotic complications 2
  • Fibrin glue may be useful for local hemostasis 2
  • Blood group O and lower levels of factor VIII/VWF may contribute to bleeding tendency in heterozygotes 3

Clinical Implications

• Risk Assessment:

  • Type 2 VWD patients may require more careful monitoring for mucocutaneous bleeding 1, 5
  • Factor XI deficient patients need particular attention before surgical procedures 2
  • Both conditions require individualized bleeding risk assessment before surgery or invasive procedures 1, 2

• Genetic Counseling:

  • Type 2 VWD is typically inherited in an autosomal dominant pattern (except Type 2N which is recessive) 6
  • Factor XI deficiency follows an autosomal recessive inheritance pattern, though heterozygotes can have bleeding symptoms 2, 3