platelet-type bleeding disorder 19

Platelet-Type Bleeding Disorder 19 (BDPLT19)

Platelet-type bleeding disorder 19, also known as BDPLT19, is a rare isolated hereditary giant platelet disorder characterized by severe thrombocytopenia and thrombopathy due to defects in proplatelet formation and platelet activation in homozygous patients [1]. This condition leads to recurrent bleeding episodes, including epistaxis (nosebleeds), spontaneous hematomas (bruises), and bleeding after minor trauma or surgical procedures [2].

The disorder is caused by mutations in the PRKACG gene, which codes for a protein involved in platelet activation and proplatelet formation [3]. These mutations can lead to a significant reduction in platelet count and function, making it difficult for the body to form blood clots and stop bleeding.

Clinical Features

The clinical features of BDPLT19 include:

• Recurrent bleeding episodes
• Epistaxis (nosebleeds)
• Spontaneous hematomas (bruises)
• Bleeding after minor trauma or surgical procedures
• Thrombocytopenia (low platelet count)

Genetic Cause

BDPLT19 is caused by mutations in the PRKACG gene, which codes for a protein involved in platelet activation and proplatelet formation [3]. These mutations can lead to a significant reduction in platelet count and function.

References

[1] Platelet-type bleeding disorder 19. MedGen UID: 863842 [2] Platelet-type bleeding disorder 19. Summary. [3] Manchev et al. (2014) identified homozygous missense mutations in the PRKACG gene in two sibs with platelet-type bleeding disorder-19.

Note: The above information is based on the search results provided and may not be a comprehensive or definitive description of BDPLT19.

Common Signs and Symptoms of Platelet-Type Bleeding Disorder

Platelet-type bleeding disorders, also known as thrombocytopenia or platelet dysfunction, can manifest in various ways. The following are some common signs and symptoms:

• Easy bruising: People with platelet disorders may experience easy bruising, which can appear as small red or purple spots on the skin (petechiae) [2][3].
• Abnormal bleeding: This can include nosebleeds, bleeding gums, heavy menstrual periods, and prolonged bleeding after a cut or injury [8][10].
• Blood in urine or stool: In some cases, people with platelet disorders may experience blood in their urine or stool [6][7].
• Swelling and difficulty moving: Some individuals may experience swelling and difficulty moving due to excessive bleeding [7].

Other Possible Symptoms

In addition to the above symptoms, children with platelet disorders may experience frequent bruises, nosebleeds, and bleeding in the mouth and gums [9]. Adults may also experience prolonged bleeding after a cut or other injury [10].

It's essential to note that mild thrombocytopenia often has no symptoms, but severe cases can lead to more significant complications [5].

References

[1] Mar 24, 2022 — You may have trouble stopping bleeding. Symptoms of platelet disorders include blood clots, bleeding, and bruising. [2] Symptoms and Signs of Platelet Disorders · Multiple petechiae in the skin (typically most evident on the lower legs) · Scattered small ecchymoses at sites of ... [3] Apr 19, 2022 — Petechiae · Easy or excessive bruising (purpura) · Superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple ... [4] Generally symptoms of a platelet disorder are similar, with bruising from minor trauma, bleeding from the mouth, nose or digestive system and excessive bleeding ... [5] Mar 24, 2022 — Bleeding causes the main symptoms of thrombocytopenia. Symptoms can appear suddenly or over time. Mild thrombocytopenia often has no symptoms. [6] Nov 20, 2023 — The bleeding has the characteristics of a platelet disorder, and gastrointestinal tract bleeding is the most frequent manifestation. Platelet ... [7] Apr

Diagnostic Tests for Platelet-Type Bleeding Disorder

Platelet-type bleeding disorders, also known as von Willebrand disease (VWD) type 2B, are a group of conditions characterized by abnormal platelet function. The diagnostic tests for these disorders can help identify the underlying cause of bleeding symptoms.

• Low-dose ristocetin-induced platelet aggregation: This test is used to establish the diagnosis of VWD type 2B. It measures the ability of platelets to aggregate in response to low doses of ristocetin, a medication that stimulates platelet activation.
• VWF antigen and activity levels: These tests measure the levels of von Willebrand factor (VWF) antigen and activity in the blood. Low levels or abnormal function of VWF can indicate a platelet-type bleeding disorder.
• Platelet count and morphology: A complete blood count (CBC) with a platelet count and peripheral blood smear can help identify abnormalities in platelet number and appearance, which may suggest a platelet-type bleeding disorder.

Additional Tests

If the initial tests do not confirm a platelet-type bleeding disorder, additional tests may be necessary to rule out other conditions. These may include:

• Bleeding time: A test that measures the time it takes for bleeding to stop after a small cut is made on the skin.
• Prothrombin time and activated partial thromboplastin time: Tests that measure the clotting ability of blood.

References

• [12] Testing for VWF antigen and activity levels and low-dose ristocetin-induced platelet aggregation can establish this diagnosis.
• [14] If a platelet-type bleeding disorder is suspected but not diagnosed by initial tests, or if the aggregation abnormalities suggested a secretion or dense granule problem, additional tests may be necessary.

Treatment Options for Platelet-Type Bleeding Disorder

Platelet-type bleeding disorders, also known as thrombocytopenia or platelet function disorders, can be treated with various medications to increase platelet count and prevent excessive bleeding. Here are some common treatment options:

• Medications that stimulate platelet production: Medicines such as romiplostim (Nplate), eltrombopag (Promacta) and avatrombopag (Doptelet) help bone marrow make more platelets [10]. These types of medicines can increase the risk of blood clots.
• Corticosteroids: Corticosteroids, such as prednisone, can help prevent bleeding by slowing down platelet destruction. They can lead to a higher platelet count in 2 to 3 weeks [7].
• Immunosuppressive medications: Medications like rituximab (Rituxan, Ruxience, Truxima) can help increase the platelet count by reducing the immune system response that is damaging them [9].
• Enzyme-replacement therapy: Imiglucerase is an enzyme-replacement treatment that will increase platelet levels in adults and children 2 years of age and older with Type 1 Gaucher disease [9].

Other Treatment Options

In addition to these medications, other treatments might involve:

• Blood or platelet transfusions: If your platelet level becomes too low, your doctor can replace lost blood with transfusions of packed red blood cells or platelets [11].
• Changing medications that may be causing the disorder: If a medicine is causing your platelet disorder, your healthcare provider will ask you to stop taking that medicine [1].

Important Notes

It's essential to note that treatment varies depending on the type of platelet function disorder a person has. Some medications can make platelet function and bleeding symptoms worse [6]. Therefore, it's crucial to consult with a healthcare professional for personalized advice.

References:

[1] Context 1 [7] Context 7 [9] Context 9 [10] Context 10 [11] Context 11

Differential Diagnosis of Platelet-Type Bleeding Disorder

Platelet-type bleeding disorders are a group of conditions characterized by abnormalities in platelet function or number, leading to excessive bleeding or bruising. The differential diagnosis of these disorders involves identifying the underlying cause of the bleeding symptoms.

• Thrombocytopenia: A low platelet count can be caused by various factors, including idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) [9].
• Platelet dysfunction: Abnormalities in platelet function can be caused by conditions such as Bernard-Soulier syndrome (BSS), Glanzmann's thrombasthenia, and platelet-type von Willebrand disease (vWD) [4, 49].
• Macrothrombocytopenia: A condition characterized by large platelets, which can be seen in BSS, MYH9-related disorders, and gray platelet syndrome (GPS) [14].

To differentiate these conditions, laboratory tests such as complete blood count (CBC), peripheral blood smear, and flow cytometry may be performed. For example, a CBC can help identify thrombocytopenia or macrothrombocytopenia, while a peripheral blood smear can reveal abnormalities in platelet morphology [6].

In some cases, additional tests such as GPIb/IX analysis using flow cytometry may be required to diagnose conditions like BSS [14]. It is essential to exclude other causes of thrombocytopenia, such as ITP, before considering a diagnosis of IPD [5].

The differential diagnosis of platelet-type bleeding disorders requires a comprehensive approach, including a thorough medical history, physical examination, and laboratory tests. A correct diagnosis can help guide treatment and improve patient outcomes.

References:

[4] The fact that bleeding responds to fibrinolytic inhibitors rather than platelet transfusions led to the discovery that platelets in this disorder possessed unusually large amounts of urokinase-type plasminogen activator, a protein that is released on platelet activation [4, 49].

[5] Nov 20, 2023 — The diagnosis of ITP is established by the exclusion of other causes of thrombocythemia. The peripheral blood film should be examined to rule ...

[6] Diagnosis of Platelet Disorders​​ Doctors can diagnose many platelet disorders by a simple blood test (a complete blood count [CBC]), which includes measurement ...

[9] Jan 15, 2020 — If your blood has a low number of platelets, it is called thrombocytopenia. This can be caused by various factors, including ITP, TTP, and HIT.

[14] When thrombocytopenia occurs, platelet size provides important information for differentiating some IPDs. If the patient shows macrothrombocytopenia, platelet-type vWD, BSS, MYH9-related disorders, and GPS should be considered after excluding ITP . For BSS diagnosis, platelet surface GPIb/IX analysis using flow cytometry is required .