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Questions and Answers
What is the primary difference between Hemophilia A (HA) and Von Willebrand Disease (VWD) in terms of bleeding symptoms?
What is the primary difference between Hemophilia A (HA) and Von Willebrand Disease (VWD) in terms of bleeding symptoms?
Which of the following is NOT a characteristic of Hemorrhagic Disease of the Newborn?
Which of the following is NOT a characteristic of Hemorrhagic Disease of the Newborn?
What is the mechanism of action of ristocetin in relation to Von Willebrand Factor (VWF)?
What is the mechanism of action of ristocetin in relation to Von Willebrand Factor (VWF)?
Which of the following is NOT a common cause of Vitamin K deficiency in children and adults?
Which of the following is NOT a common cause of Vitamin K deficiency in children and adults?
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Which treatment is generally recommended for Type 1 Von Willebrand Disease?
Which treatment is generally recommended for Type 1 Von Willebrand Disease?
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Which of the following is a potential consequence of Vitamin K deficiency in newborns?
Which of the following is a potential consequence of Vitamin K deficiency in newborns?
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What is the primary function of Von Willebrand Factor (VWF) in hemostasis?
What is the primary function of Von Willebrand Factor (VWF) in hemostasis?
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Which of the following laboratory findings is NOT typically seen in Vitamin K deficiency?
Which of the following laboratory findings is NOT typically seen in Vitamin K deficiency?
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What is the primary factor deficient in Hemophilia A?
What is the primary factor deficient in Hemophilia A?
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How is Hemophilia A inherited?
How is Hemophilia A inherited?
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What manifestation is commonly associated with Hemophilia A in infants?
What manifestation is commonly associated with Hemophilia A in infants?
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Which of the following conditions is a rare complication of Hemophilia?
Which of the following conditions is a rare complication of Hemophilia?
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What is the relationship between FVIII levels and the severity of Hemophilia A?
What is the relationship between FVIII levels and the severity of Hemophilia A?
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Which laboratory test is NOT part of the initial workup for Hemophilia A?
Which laboratory test is NOT part of the initial workup for Hemophilia A?
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Which type of bleeding is particularly characteristic of Hemophilia?
Which type of bleeding is particularly characteristic of Hemophilia?
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In the context of Hemophilia, what is meant by 'hemarthrosis'?
In the context of Hemophilia, what is meant by 'hemarthrosis'?
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What is the initial laboratory finding indicative of hemophilia A or B?
What is the initial laboratory finding indicative of hemophilia A or B?
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What does a mixing study following a prolonged PTT indicate?
What does a mixing study following a prolonged PTT indicate?
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What is the suggested next step after performing a mixing study if factor deficiency is suspected?
What is the suggested next step after performing a mixing study if factor deficiency is suspected?
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Which method can be used for antenatal diagnosis of hemophilia?
Which method can be used for antenatal diagnosis of hemophilia?
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What role does desmopressin play in the treatment of hemophilia?
What role does desmopressin play in the treatment of hemophilia?
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Which condition would be considered when factor VIII activity is less than 40% of normal?
Which condition would be considered when factor VIII activity is less than 40% of normal?
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In which scenario would low levels of factor IX at birth not indicate the presence of hemophilia B?
In which scenario would low levels of factor IX at birth not indicate the presence of hemophilia B?
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What is the primary characteristic of acquired hemophilia A?
What is the primary characteristic of acquired hemophilia A?
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What is the primary consequence of impaired absorption of Vitamin K in cases of biliary obstruction?
What is the primary consequence of impaired absorption of Vitamin K in cases of biliary obstruction?
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Which condition is NOT a trigger for the entry of procoagulant material into circulation leading to disseminated intravascular coagulation?
Which condition is NOT a trigger for the entry of procoagulant material into circulation leading to disseminated intravascular coagulation?
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Which of the following is a laboratory finding associated with disseminated intravascular coagulation?
Which of the following is a laboratory finding associated with disseminated intravascular coagulation?
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What leads to thrombocytopenia in patients with liver disease?
What leads to thrombocytopenia in patients with liver disease?
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What is a characteristic feature of disseminated intravascular coagulation (DIC)?
What is a characteristic feature of disseminated intravascular coagulation (DIC)?
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Which treatment option is appropriate for managing disseminated intravascular coagulation?
Which treatment option is appropriate for managing disseminated intravascular coagulation?
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How does the secretion of thromboplastin by damaged liver cells contribute to DIC?
How does the secretion of thromboplastin by damaged liver cells contribute to DIC?
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Which mechanism contributes to hemolytic anemia in DIC?
Which mechanism contributes to hemolytic anemia in DIC?
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Which of these statements correctly compares Hemophilia B and Von Willebrand's Disease (VWD)?
Which of these statements correctly compares Hemophilia B and Von Willebrand's Disease (VWD)?
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What is a common manifestation of both Hemophilia B and Von Willebrand's Disease (VWD)?
What is a common manifestation of both Hemophilia B and Von Willebrand's Disease (VWD)?
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Which type of Von Willebrand's Disease (VWD) is characterized by the presence of very little or total lack of von Willebrand factor (vWF)?
Which type of Von Willebrand's Disease (VWD) is characterized by the presence of very little or total lack of von Willebrand factor (vWF)?
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Which of these statements accurately describes the function of von Willebrand factor (vWF)?
Which of these statements accurately describes the function of von Willebrand factor (vWF)?
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Which type of Von Willebrand's Disease (VWD) is associated with abnormally high affinity of von Willebrand factor (vWF) for platelets, leading to abnormal vWF attachment to platelets even in the absence of injury?
Which type of Von Willebrand's Disease (VWD) is associated with abnormally high affinity of von Willebrand factor (vWF) for platelets, leading to abnormal vWF attachment to platelets even in the absence of injury?
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Hemophilia is a hereditary disease, but it can also be caused by:
Hemophilia is a hereditary disease, but it can also be caused by:
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Which of these laboratory tests is used to assess the concentration of von Willebrand factor (vWF) protein in plasma?
Which of these laboratory tests is used to assess the concentration of von Willebrand factor (vWF) protein in plasma?
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In which type of Von Willebrand's Disease (VWD) is the platelet count typically low?
In which type of Von Willebrand's Disease (VWD) is the platelet count typically low?
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Flashcards
Hemophilia
Hemophilia
A bleeding disorder caused by deficiencies in blood clotting factors.
Hemophilia A
Hemophilia A
A subtype of hemophilia linked to a deficiency of Factor VIII (FVIII).
Hemophilia B
Hemophilia B
A subtype of hemophilia linked to a deficiency of Factor IX (FIX).
Von Willebrand's Disease
Von Willebrand's Disease
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X-Linked Recessive Inheritance
X-Linked Recessive Inheritance
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Clinical Features of Hemophilia A
Clinical Features of Hemophilia A
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Laboratory Tests for Hemophilia
Laboratory Tests for Hemophilia
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Factor VIII Levels
Factor VIII Levels
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Prolonged PTT
Prolonged PTT
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Mixing study
Mixing study
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Factor VIII diagnosis
Factor VIII diagnosis
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Carrier detection
Carrier detection
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Desmopressin
Desmopressin
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Acquired hemophilia A
Acquired hemophilia A
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Umbilical cord blood samples
Umbilical cord blood samples
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Von Willebrand's Disease (vWD)
Von Willebrand's Disease (vWD)
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Types of vWD
Types of vWD
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Laboratory findings in vWD
Laboratory findings in vWD
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vWF function
vWF function
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Specialized lab investigation for vWD
Specialized lab investigation for vWD
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Bleeding symptoms in vWD
Bleeding symptoms in vWD
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Ristocetin
Ristocetin
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Symptoms of Hemophilia A
Symptoms of Hemophilia A
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Vitamin K Deficiency
Vitamin K Deficiency
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Hemorrhagic Disease of the Newborn
Hemorrhagic Disease of the Newborn
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Treatments for Vitamin K Deficiency
Treatments for Vitamin K Deficiency
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Prophylaxis for Coagulation Disorders
Prophylaxis for Coagulation Disorders
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Vitamin K Absorption Issues
Vitamin K Absorption Issues
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Thrombocytopenia in Liver Disease
Thrombocytopenia in Liver Disease
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Dysfibrinogenaemia
Dysfibrinogenaemia
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DIC Pathogenesis
DIC Pathogenesis
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DIC Laboratory Findings
DIC Laboratory Findings
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Fresh Frozen Plasma Treatment
Fresh Frozen Plasma Treatment
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Causes of DIC
Causes of DIC
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Study Notes
Coagulation Disorders
- Coagulation disorders are conditions affecting the blood's ability to clot.
Inherited Coagulation Disorders: Overview
- Hemophilia
- Hemophilia A is a deficiency of Factor VIII.
- Hemophilia B is a deficiency of Factor IX.
- von Willebrand's Disease
- Types 1-3 involve a lack or reduced production of von Willebrand Factor (vWF).
Hemophilia
- Also known as "love of bleeding."
- Bleeding symptoms in Hemophilia A and B are similar.
- Some infants are asymptomatic until experiencing minor trauma.
- Bruising and spontaneous bleeding (joints, muscles, soft tissues) are common.
- Life-threatening bleeding can occur after trauma or surgery, leading to lifelong bleeding problems.
Hemophilia A
- Bleeding is due to a deficiency of Factor VIII coagulant activity.
- Bleeding severity is linked to Factor VIII levels in the blood.
- Low Factor VIII levels (<1 IU/dL) lead to frequent bleeding, including spontaneous bleeding into joints or muscles.
- Inheritance is recessive X-linked.
- Males are affected, and females are carriers.
- Gene mutation causes Factor VIII production defects (absence/low level of plasma factor VIII).
X-linked Recessive Inheritance (Hemophilia)
- Unaffected fathers pass on the normal X chromosome.
- Carrier mothers pass on either the affected or normal X chromosome.
Clinical Features of Hemophilia A
- Infants may develop joint and soft tissue bleeding and excessive bruising.
- Dental extraction can result in prolonged bleeding.
- Hemarthrosis (recurrent bleeding into joints) causes pain and joint deformity; Poorly treated hematomas lead to joint deformity and disability.
- Hemophilic pseudo tumor is a rare complication - leading to progressive swelling of muscles and/or bone due to repeated bleeding.
- Hematuria (blood in urine) and gastrointestinal bleeding are possible.
Severity of Hemophilia A relates to Factor VIII
- Severe: Factor level 0-1 IU/dL - Spontaneous bleeding; severe bleeding.
- Moderate: Factor level 2-5 IU/dL - Few bleeds; hemarthroses; mainly traumatic.
- Mild: Factor level 5-30 IU/dL - Post-traumatic; post-surgical; post-dental extraction; few episodes.
Coagulation Pathway
- Intrinsic pathway (activated by injury or blood contact).
- Extrinsic pathway (activated by tissue trauma).
- Common pathway (converges to form fibrin).
- Activated partial thromboplastin time (aPTT) and prothrombin time (PT).
- Thrombin time (TT) helps form fibrin clot from fibrinogen.
Laboratory Investigations (Hemostasis tests) for Hemophilia A
- Initial work includes complete blood count, prothrombin time (PT), partial thromboplastin time (PTT), bleeding time (BT).
- PTT is usually prolonged in both Hemophilia A and B.
- PT and bleeding time are usually normal in both conditions.
- Mixing studies can help distinguish between factor deficiencies and inhibitors.
- Factor VIII activity levels below 40% of normal often suggest Hemophilia A.
- Molecular genotyping confirms the diagnosis and severity prediction.
Other Laboratory Investigation (Carrier Detection) & Antenatal Diagnosis
- Measuring plasma Factor VIII levels.
- DNA probes detect mutations in carriers can help detect mutations if known.
- 8-10 weeks gestation biopsies of the fetus; Fetal DNA analysis at 16-20 weeks of gestation, through Ultrasound Guided Needle Aspiration.
Treatments for Hemophilia A
- Factor VIII replacement therapy using recombinant factor or frozen plasma concentrates.
- Desmopressin, a synthetic vasopressin analogue, releases Factor VIII and vWF, boosting plasma levels.
- Prophylactic treatments, storing Factor VIII at home, reduce bleeding episodes and hospitalizations, improving quality of life.
Non-Genetic Form of Hemophilia A
- Caused by autoantibodies against Factor VIII (acquired hemophilia A).
- Associated with cancers, autoimmune disorders, and postpartum conditions.
Hemophilia B
- Also known as Christmas disease.
- Factor IX deficiency.
- Clinical features are identical to Hemophilia A.
- Distinguished by specific coagulation assays.
- Incidence is approximately 1 in 5 of Hemophilia A.
- Similar carrier and antenatal diagnosis protocol as in Hemophilia A, but factor IX levels at birth may take up to 6 months to reach normal levels.
Treatments for Hemophilia B (Laboratory Findings)
- Infusion of Factor IX, with its longer half-life, reduces infusion frequency compared to Factor VIII.
- Prolonged aPTT, reduced FIX clotting assay, normal bleeding time, normal PT.
Additional Information for Hemophilia
- Hemophilia is often hereditary but may also arise from spontaneous mutations.
- Caused by defect/mutation in clotting factor genes.
- Over 1,000 mutations in factor VIII and IX genes are identified.
- Females are primarily carriers, but can present with or without symptoms.
Von Willebrand's Disease
- Abnormalities due to either reduced levels or abnormal functions of von Willebrand Factor (vWF); caused by point mutation or large deletion.
- vWF large proteins (300 kDa) form multimers.
- Inheritance is autosomal dominant.
- Typically involves mucosal bleeding, bleeding after dental extraction and post-traumatic hemorrhage.
- Severity of disease varies.
vWF - Dwifunctional proteins
- Promoters platelet adhesion to damaged endothelium and platelet aggregation.
- Acts as carrier molecule for Factor VIII - protecting it from premature destruction; thus there are reduced Factor VIII in vWD disease.
vWD 3 Types:
- Type 1: Reduced vWF – milder form of disease.
- Type 2: Abnormal structure of vWF (reduced function).
- 2A – Loss of high-molecular-weight multimers of vWF. -2B – vWF has abnormally high affinity for platelets, causing early platelet clumping (thrombocytopenia may be present) and problems with vWF's role in clotting. -2M – Defective GPIb binding site, preventing vWF attachment to platelets (inhibiting aggregation). -2N – Reduced affinity for Factor VIII, thus preventing its protection from destruction.
- Type 3: Very little or no vWF – most severe form of the disease.
Von Willebrand's Disease: Laboratory Findings
- Prolonged bleeding time
- Low Factor VIII
- Prolonged aPTT
- Low vWF
- Defective platelet aggregation
- Platelet counts-normal, except possible low counts in type 2B.
Specialized Lab Investigations for vWF
- vWF:Ag (immunoassay) measures vWF protein concentration in plasma
- VWF:RCo (ristocetin cofactor activity) measures vWF's interaction with platelets.
Treatments for Von Willebrand's Disease
- Antifibrinolytic agents (Type 2B)
- Desmopressin (Type 1).
- Factor VIII and vWF infusions (for patients with very low vWF levels).
Hemophilia A vs VWD: Differences
- Gender: Hemophilia A is mainly in males, while VWD affects both genders.
- Bleeding Symptoms: Hemophilia A often involves deep tissue bleeding (joints, internal organs); VWD primarily involves mucosal bleeding (nose, mouth, vagina).
Acquired Coagulation Disorders
- More common than inherited disorders.
- Involves deficiencies caused by multiple clotting factors (often not well specified).
Vitamin K Deficiency
- Causes: Inadequate diet, malabsorption, vitamin K antagonist drugs (like warfarin).
- Effects: Decreased functional activity of factors II, VII, IX, X; protein C & S; may be present in newborns.
- hemorrhagic disease of the new born.
Hemorrhagic Disease of the Newborn
- Vitamin K Deficiency that can present as hemorrhagic episodes in newborns.
- Causes: Liver cell immaturity (cannot absorb vitamin K), lack of gut bacteria for vitamin K synthesis, low vitamin K quantities in breast milk.
- Symptoms: Hemorrhage symptoms.
- Laboratory findings: Prolonged PT and aPTT; Normal Platelet count and fibrinogen levels; Deficiency of vitamin K dependent procoagulants factors II, VII, IX, X.
Vitamin K Deficiency in Liver Diseases
- Causes: Obstructive jaundice, pancreatic or small bowel disease.
- Laboratory findings: Prolonged PT and aPTT; Normal Platelet count and fibrinogen levels; Deficiency of vitamin K dependent procoagulants factors II, VII, IX, X.
Hemostasis Disorders in Liver Diseases
- Liver disease impacts multiple aspects of hemostasis (absorption and synthesis, coagulation factors, fibrinogen, inhibitors).
- Vitamin K absorption and coagulation factors synthesis are decreased.
- Fibrinogen synthesis is affected (acquired dysfibrinogenemia).
- Thrombopoietin production decreases (thrombocytopenia).
- Elevated procoagulant release (DIC).
Liver Diseases
- Biliary obstruction: Impaired vitamin K absorption, and reduced synthesis of factors II, VII, IX, and X by liver parenchymal cells.
- Severe hepatocellular diseases: Functional abnormality of fibrinogen (dysfibrinogenemia), and decreased thrombopoietin production leading to thrombocytopenia; DIC (due to thromboplastin secretion by damaged liver cells).
Disseminated Intravascular Coagulation (DIC)
- Widespread intravascular fibrin deposition. Over-consumption of clotting factors and platelets. Caused by release of procoagulants into circulation, and endothelial damage/activation.
- Pathogenesis: Amniotic fluid embolism, liver disease, placental separation, cancer cells, snake bites, endothelial damage, infections, autoimmune response (vasculitis), severe burns.
- Laboratory findings: Low platelet counts, prolonged prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), elevated D-dimers or fibrin degradation products (FDPs); hemolytic anemia with red blood cell (RBC) fragmentation.
Treatments for DIC
- Fresh Frozen Plasma (FFP)
- Red Blood Cell (RBC) transfusion
- Antithrombin and protein C to inhibit DIC
Coagulation Deficiency Caused by Antibodies
- Alloantibodies to factor VIII are found in 5-10% hemophilia cases.
- SLE/ auto-immune disease and lupus anticoagulant interfere with coagulation.
- Treatment involves Immunosuppression or factor replacement.
Massive Transfusion Syndrome
- Dilution of reduced platelets and coagulation inhibitors (due to blood storage at 4C).
- Poor function and low counts of blood platelets.
- Possible pre-existing bleeding disorders
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Description
Test your knowledge on the differences between Hemophilia A and Von Willebrand Disease as well as understand Vitamin K deficiency and related treatments. This quiz covers important concepts in hemostasis critical for medical professionals and students alike.
