Thrombocytopenia Flashcards
outline the four main processes that can lead to a decrease in platelet counts below 150 x 10^9/L
Failure of Marrow Production:
Cause: Various factors can impair platelet production in the bone marrow, including conditions like leukemia, myelodysplasia, aplastic anemia, certain drugs, megaloblastic anemia, malignant infiltration of the marrow, and infections.
Notes: This process usually results in pancytopenia, a reduction in the counts of all blood cell types, and is often an early sign of bone marrow suppression.
Shortened Lifespan:
Cause: Platelets can have a reduced lifespan in the bloodstream due to conditions such as immune thrombocytopenic purpura (ITP), certain drugs, connective tissue disorders, antiphospholipid antibody syndrome, infections, and disseminated intravascular coagulation (DIC).
Notes: Platelets are typically destroyed by the immune system while they are in circulation in these cases.
Sequestration:
Cause: Platelets may be sequestered or pooled in the spleen. This can occur in conditions like hypersplenism (enlarged spleen) or after cardiopulmonary bypass surgery.
Notes: Platelets accumulate in the spleen rather than circulating in the bloodstream.
Dilution:
Cause: Platelet counts may appear low due to the dilution of the blood with large-volume blood transfusions. This can occur in cases of massive blood transfusion, particularly when packed red blood cells are administered.
Notes: The platelet count is seemingly reduced because the transfusions consist mainly of packed red cells, which dilute the blood.
give an overview of autoimmune thrombocytopenia
Previous Terminology: ITP was previously known as idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura. The name change reflects the evolving understanding of the condition, as it’s no longer considered truly “idiopathic” (without a known cause) due to the recognized immune mechanisms involved.
Age and Gender Prevalence: ITP can affect both children and adults, but it is more commonly seen in young female adults. In children, it’s often acute and self-limited, while in adults, it may be persistent or chronic.
Immune Mechanisms: In ITP, the immune system produces antibodies directed against platelet antigens, leading to the destruction of platelets in the bloodstream. Alternatively, T-cell-mediated autoimmunity can also play a role in platelet destruction.
Clinical Presentation: Patients with ITP may present with petechiae, purpura, and bruising due to the low platelet count. Severe cases can lead to bleeding symptoms, such as nosebleeds, gum bleeding, or heavy menstrual periods.
Heterogeneous Nature: ITP can manifest in various ways, and it can be:
An isolated condition, where it affects platelet counts but is not associated with other autoimmune diseases.
A feature of an autoimmune disease, where ITP is part of a broader autoimmune disorder.
A complication of chronic lymphocytic leukemia or lymphoma.
Associated with other autoimmune hematological disorders, such as autoimmune hemolytic anemia or autoimmune neutropenia.
The treatment of ITP varies depending on the severity and clinical presentation. Therapeutic options may include medications that modulate the immune system, such as corticosteroids, intravenous immunoglobulin (IVIG), and immunosuppressive drugs. In some cases, a splenectomy (surgical removal of the spleen) may be considered to improve platelet counts. Management decisions are typically made based on individual patient characteristics and clinical assessment.
explain acute immune thrombocytopenic purpura (ITP)
Characteristics of Acute ITP: Onset: Acute ITP often occurs in childhood, with an abrupt onset typically about one week after a trivial viral illness. This rapid onset is a distinguishing feature. Pathogenesis: It is believed that in acute ITP, post-viral IgG antibodies attach to viral antigens that have been absorbed onto the surface of platelets. This immune reaction leads to the destruction of platelets. Platelet Count: Platelet levels rapidly fall to very low counts, often as low as 20 x 10^9/L. Despite the low platelet count, intracranial bleeding (bleeding inside the skull) is rare in acute ITP. Self-Limiting: Acute ITP is typically self-limiting, meaning that it tends to resolve on its own without specific treatment. In many cases, the platelet count returns to normal within a few weeks or months. Management: In cases where treatment is needed to raise the platelet count or manage bleeding, options may include oral steroids or intravenous immunoglobulin (IVIG). These treatments can help increase platelet counts more rapidly. Chronic ITP: Although most cases of acute ITP resolve, some children may progress to chronic ITP. However, chronic ITP in children is relatively benign, and it often resolves eventually.
explain chronic immune thrombocytopenic purpura (ITP)
Disease Mechanisms: In chronic ITP, the immune-mediated destruction of platelets is a common feature, often involving antibodies directed against platelet antigens. However, it’s worth noting that some cases of chronic ITP do not respond to standard immunosuppressive therapy, suggesting alternative immune mechanisms. Recent research has shown that in some instances, there can be damage to megakaryocytes (the cells that produce platelets) and/or interference with platelet production.
Age Prevalence: Chronic ITP is more commonly seen in adulthood than in childhood. It is a condition that can persist for an extended period, often exceeding six months.
Clinical Presentation: Patients with chronic ITP may be asymptomatic or have insidious, gradual-onset bleeding symptoms. Serious bleeding events are relatively rare and typically occur when platelet counts drop below 10 x 10^9/L. Fatigue is a common symptom associated with chronic ITP.
Splenomegaly and Platelet Size: The presence of a palpable spleen (splenomegaly) suggests that the diagnosis might be something other than ITP. It’s important to differentiate ITP from other conditions that could cause similar symptoms.
Platelet Characteristics: In chronic ITP, platelets may be larger than normal (macroplatelets). This can be an important characteristic in the evaluation of chronic ITP.
Differential Diagnosis: In cases of chronic thrombocytopenia, healthcare providers need to rule out other conditions that could be causing low platelet counts, such as disseminated intravascular coagulation (DIC) and autoimmune disorders like systemic lupus erythematosus (SLE).
Platelet Transfusion: Platelet transfusions are typically reserved for life-threatening bleeding episodes. They are not a routine treatment for chronic ITP due to the underlying immune mechanisms that lead to platelet destruction.
Management of chronic ITP often involves a tailored approach based on individual patient characteristics and platelet counts. Treatment may include medications that suppress the immune system, such as corticosteroids
explain the hallmark features of TTP
The combination of fever, fluctuating neurological symptoms, thrombocytopenia (often severe), hemolytic anemia, and renal impairment is characteristic of a condition known as Thrombotic Thrombocytopenic Purpura (TTP).
TTP is a rare but serious medical emergency that results from the formation of small blood clots throughout the body’s small blood vessels, leading to a range of symptoms and potential organ damage. These are the hallmark features of TTP:
Fever: Patients with TTP may develop a fever as a result of the underlying inflammatory and clotting processes.
Fluctuating Neurological Symptoms: Neurological symptoms can vary and include confusion, cognitive changes, seizures, and in severe cases, coma. These symptoms arise because the small clots can affect blood flow to the brain.
Thrombocytopenia: Thrombocytopenia refers to a low platelet count. In TTP, this is often severe, leading to an increased risk of bleeding and bruising.
Hemolytic Anemia: Hemolytic anemia occurs when red blood cells are destroyed faster than they can be produced, leading to anemia. In TTP, the small clots can damage red blood cells, causing hemolysis.
Renal Impairment: Kidney damage can occur as a result of the small blood clots blocking blood vessels in the kidneys, leading to reduced kidney function.
explain Hemolytic Uremic Syndrome (HUS)
The combination of hemolytic anemia and renal impairment is characteristic of a condition known as Hemolytic Uremic Syndrome (HUS). HUS is a rare but serious condition that primarily affects the blood and blood vessels.
Key features of HUS include:
Hemolytic Anemia: HUS often presents with the destruction of red blood cells (hemolysis), leading to anemia. Hemolysis can occur because of the damage to red blood cells as they pass through small blood vessels.
Renal Impairment: HUS can lead to renal (kidney) impairment, which is one of the distinguishing features of the syndrome. The small blood clots that form in the body’s blood vessels can block blood flow to the kidneys, causing kidney damage and impaired kidney function.
HUS can be further categorized into two main types:
Typical HUS: Typically associated with an infection, often caused by certain strains of Escherichia coli (E. coli), particularly O157:H7. It is more common in children and often follows a diarrheal illness.
Atypical HUS: Atypical HUS is a less common form that is not always associated with an infection. It often has a genetic or inherited component and can affect individuals of all ages, including adults.
The treatment for HUS may involve supportive care, such as maintaining hydration and addressing kidney function, in addition to specific therapies in some cases. It’s important to recognize the symptoms of HUS and seek medical attention promptly, as early intervention can improve outcomes.
explain the key points of Thrombotic Thrombocytopenic Purpura (TTP)
The condition you’re describing is Thrombotic Thrombocytopenic Purpura (TTP), which results from a deficiency of a von Willebrand factor-cleaving protease, also known as ADAMTS13. TTP can occur due to the presence of an autoantibody against ADAMTS13, leading to impaired cleavage of ultra-large von Willebrand factor (vWF) molecules. Here are the key points:
ADAMTS13 Deficiency: TTP is primarily characterized by a deficiency of ADAMTS13, a protease responsible for cleaving large vWF multimers into smaller, more functional forms. In TTP, the presence of an autoantibody inhibits ADAMTS13 activity, resulting in the accumulation of ultra-large vWF molecules.
Von Willebrand Factor and Platelet Adhesion: These ultra-large vWF molecules, when unregulated, lead to excessive platelet adhesion to endothelial surfaces. This can cause the formation of small blood clots (microthrombi) in small blood vessels, which subsequently leads to the classic features of TTP.
Acquired or Inherited: TTP can occur in both acquired and inherited forms. Acquired TTP is more common and often associated with the development of autoantibodies against ADAMTS13. Inherited TTP, also known as congenital or Upshaw-Schulman syndrome, is much rarer and typically involves mutations in the ADAMTS13 gene.
Clinical Presentation: TTP is characterized by a pentad of clinical features: thrombocytopenia (low platelet count), microangiopathic hemolytic anemia (destruction of red blood cells), neurological symptoms, renal dysfunction, and fever. The presence of these features, along with ADAMTS13 deficiency, is indicative of TTP.
Treatment: The primary treatment for TTP involves plasma exchange (plasmapheresis) to remove the autoantibodies and replace the deficient ADAMTS13. Corticosteroids and immunosuppressive medications may also be used to suppress autoantibody production. The mortality rate of TTP has improved with early diagnosis and treatment, but it can still be life-threatening, with mortality rates of 10-20% even with aggressive therapy.
