Disorders of Primary Hemostasis

In vascular disorders, what general lab tests typically show normal results?

Platelet count, Platelet function test, Coagulation test

What are the vascular disorders?

Hereditary Hemorrhagic Telangiectasia, Ehlers-Danlos Syndrome, Henoch-Schonlein Purpura, Scurvy

What is another name for Hereditary Hemorrhagic Telangiectasia?

Rendu-Osler-Weber Syndrome

What is the most common inherited vascular bleeding disorder?

Hereditary Hemorrhagic Telangiectasia (Rendu-Osler-Weber Syndrome)

What is the mode of inheritance for Hereditary Hemorrhagic Telangiectasia?

autosomal dominant

What is the main vascular abnormality in Hereditary Hemorrhagic Telangiectasia?

localized dilation of capillary walls

Which areas are primarily affected by the capillary dilations in Hereditary Hemorrhagic Telangiectasia?

skin and mucous membranes

What is another name for Ehlers-Danlos Syndrome?

Cutis Hyperelastica

What are some key features of Ehlers-Danlos Syndrome?

Hyperextensible skin, hypermobile joints, joint laxity, fragile tissues, and subcutaneous hematomas

What are other names for Henoch-Schönlein Purpura?

Allergic Purpura or Nonthrombocytopenic Purpura

Who is most commonly affected by Henoch-Schönlein Purpura?

Children

What are common symptoms of Henoch-Schönlein Purpura?

gastrointestinal hemorrhage and joint swelling

What causes vascular abnormalities in Henoch-Schönlein Purpura?

immunologic damage to endothelial cells

What is another name for Scurvy?

Vitamin C (Ascorbic acid) deficiency

What causes bleeding in Scurvy?

defective synthesis of collagen and hyaluronic acid

What are the four categories in Thrombocytopenia?

1. Impaired or decreased platelet production

2. Increased platelet destruction

3. Increased splenic sequestration

4. Massive blood transfusions

What are the example of conditions with impaired or decreased platelet production?

1. Bernard-Soulier syndrome

2. Fanconi anemia

3. TAR (Thrombocytopenia with Absent Radius) syndrome

4. Viral infections

5. Leukemia

6. Megaloblastic anemia

7. Wiskott-Aldrich syndrome

8. MYH9 gene mutations

What are the examples of conditions with: Increased Platelet Destruction

1. HUS (hemolytic uremic syndrome)

2. DIC (disseminated intravascular coagulation)

3. ITP (immune thrombocytopenic purpura)

4. TTP (thrombotic thrombocytopenic purpura)

5. HIT (heparin-induced thrombocytopenia)

What happens when platelets are activated by heparin-independent IgG antibodies against a complex of heparin and PF-4?

HIT (heparin-induced thrombocytopenia)

What are the examples of conditions with: Increased Splenic Sequestration?

1. Gaucher disease

2. Hodgkin’s disease

3. Sarcoidosis

4. Lymphoma

5. Cirrhosis of the liver

6. Portal hypertension

What is another name for Reactive Thrombocytosis?

Secondary thrombocytosis

What is another name for Autonomous Thrombocytosis?

Primary thrombocytosis

How is platelet count typically affected in Reactive Thrombocytosis?

Moderately increased platelet count

How is platelet count typically affected in Autonomous Thrombocytosis?

Markedly increased platelet count

Name three clinical situations associated with Reactive Thrombocytosis.

recovery from splenectomy, acute blood loss, major surgery

Name four conditions associated with Autonomous Thrombocytosis.

essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, primary myelofibrosis

What do you call a group of malignant neoplasms involving clonal proliferations of bone marrow stem cells?

Myeloproliferative Neoplasms (MPNs)

What is a hallmark feature of MPNs in the peripheral blood?

elevations in one or more myeloid cell types.

What type of disorder is Essential Thrombocythemia (ET)?

Myeloproliferative Neoplasm (MPN)

What is a key bone marrow finding in Essential Thrombocythemia?

uncontrolled proliferation of bone marrow megakaryocytes

What is a typical platelet count in Essential Thrombocythemia?

platelet count exceeding 1 million/uL

What are the conditions associated with platelet adhesion disorder?

Bernard Soulier Syndrome, von Willebrand’s Disease

What is the primary platelet surface receptor involved for VWF?

GP Ib/IX/V

What is the deficiency in Bernard-Soulier Syndrome (BSS)?

GP Ib/IX/V

What is the inheritance pattern of Bernard-Soulier Syndrome (BSS)?

autosomal recessive trait

What are the key laboratory findings in Bernard-Soulier Syndrome (BSS)?

Low platelet count, giant platelets

What is the result of A.C.E. aggregation studies in Bernard-Soulier Syndrome (BSS)?

normal

What is the result of ristocetin aggregation studies in Bernard-Soulier Syndrome (BSS)?

abnormal

What is the most common congenital bleeding disorder?

von Willebrand Disease

What deficiency is associated with von Willebrand Disease?

VWF

What is the Prothrombin Time result in someone with VWD (Von Willebrand Disease)?

normal

What is the APTT result in someone with VWD (Von Willebrand Disease)?

prolonged

What is the result of A.C.E. aggregation studies in VWD?

normal

What is the result of ristocetin aggregation studies in VWD?

abnormal

What is the bleeding time for Type I Von Willebrand’s Disease (VWD)?

Normal or Increased

What is the bleeding tendency for Type I Von Willebrand’s Disease (VWD)?

mild

Does px with Type I Von Willebrand’s Disease (VWD) manifests petechiae?

No

What is the bleeding time for Type II Von Willebrand’s Disease (VWD)?

increased

What is the bleeding tendency for Type II Von Willebrand’s Disease (VWD)?

moderate

Does Type II Von Willebrand’s Disease (VWD) have petechiae?

none

What is the bleeding time for Type III Von Willebrand’s Disease (VWD)?

increased

What is the bleeding tendency for Type III Von Willebrand’s Disease (VWD)?

often severe

Does Type III Von Willebrand’s Disease (VWD) have petechiae?

occasionally

What is the most common variant of VWD?

Type 1

What is the mildest form of VWD?

Type 1

What is the rarest type of VWD?

Type 3

What is the most severe form of VWD?

Type 3

What are the examples of conditions with platelet aggregation disorder?

glanzmann’s thrombasthenia, hereditary afibrogenemia

What complex is deficient in Glanzmann’s thrombasthenia?

GP IIb/IIIa

What inheritance pattern is associated with glanzmann’s thrombasthenia?

Autosomal recessive

What is the bleeding time of patients with glanzmann’s thrombasthenia?

Very prolonged

What is the result of clot retraction in patients with glanzmann’s thrombasthenia?

Abnormal

What is the result of aggregation response in A. C. E. in patients with Glanzmann’s Thrombasthenia?

Abnormal

What is the aggregation response in ristocetin in patients with Glanzmann’s Thrombasthenia?

Normal

What do you call the disorder where there is an absence of fibrinogen in the blood?

Hereditary afibrinogenemia

What is the platelet fibrinogen receptor?

GP IIb/IIIa

What do you call the process where in platelets adhere to other platelets?

aggregation

What are some examples of conditions with platelets secretion disorder?

Thromboxane pathway disorders, cyclooxygenase or thromboxane synthetase deficiency, storage pool diseases

What granule is deficient in gray platelet syndrome?

Alpha

What is the inheritance pattern of gray platelet syndrome?

Autosomal recessive

What type of bleeding tendency is seen in Gray Platelet Syndrome?

lifelong mild bleeding tendencies

What level of thrombocytopenia is seen in Gray Platelet Syndrome?

Moderate thrombocytopenia

What bone marrow finding is associated with Gray Platelet Syndrome?

marrow fibrosis

What is the appearance of platelets in Gray Platelet Syndrome?

Large, gray platelets

What happens to plasma levels of PF-4 and β-thromboglobulin in Gray Platelet Syndrome?

Increased

What are some examples of dense granule deficiencies?

Hermansky- Pudlak syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich syndrome, TAR syndrome

Which type of dense granule deficiencies exhibit albinism?

Hermansky- Pudlak syndrome, Chediak-Higashi syndrome

What type of albinism does Hermansky- Pudlak Syndrome manifest?

oculocutaneous

What type of albinism does Chediak-Higashi Syndrome manifest?

Partial albinism

What are the syndromes associated with dense granule deficiencies which does not exhibit albinism?

WAS, TAR Syndrome

What is the platelet count of Hermansky- Pudlak syndrome?

normal

What is the platelet count of Chediak Higashi Syndrome?

low

What is the platelet count of WAS?

low

What is the platelet count of TAR Syndrome in infancy?

low

What is the platelet count of TAR Syndrome in infancy?

low

What is the platelet count of TAR Syndrome within 1 year of birth?

Normal

What is the inheritance pattern of these dense granule deficiencies: Hermansky- Pudlak syndrome, Chediak-Higashi syndrome, TAR syndrome?

Autosomal recessive

What is the inheritance pattern of WAS?

X-linked recessive