Thrombocytopenia Review (ITP, TTP, HUS, DIC, HIT) | Mnemonics And Proven Ways To Memorize

Thrombocytopenia Overview

Thrombocytopenia is a hematological condition characterized by abnormally low levels of platelets (thrombocytes) in the blood, measured as a platelet count of less than 150,000 platelets per microliter. This condition can lead to significant health issues, including an increased risk of bleeding, bruising, and clotting disorders, which may pose serious complications if not managed effectively.

Thrombotic Thrombocytopenic Purpura (TTP)

Definition:

Thrombotic Thrombocytopenic Purpura (TTP) is a catastrophic thrombotic microangiopathy that occurs due to a severe deficiency or inhibition of the ADAMTS-13 protease, which is essential for the degradation of von Willebrand factor (vWF).

Pathophysiology:

• A deficiency in ADAMTS-13 leads to the accumulation of large multimers of vWF in circulation.

• Increased vWF causes excessive aggregation of platelets, leading to the formation of small vessel thrombi, thrombocytopenia, and associated microangiopathic hemolytic anemia (MAHA).

Key Components:

Von Willebrand Factor (vWF):

• A large glycoprotein that plays a critical role in hemostasis by mediating platelet adhesion at sites of vascular injury.

• While vWF is essential for normal clot formation, its excessive activation resulting from ADAMTS-13 deficiency can lead to pathological thrombus formation and resultant tissue ischemia.

ADAMTS-13:

• A metalloprotease that specifically cleaves vWF, thereby regulating its activity to prevent the over-aggregation of platelets.

• Insufficient levels of ADAMTS-13 result in uncontrolled vWF activity, leading to the formation of microthrombi that obstruct blood vessels, in turn causing tissue damage and ischemia.

Clinical Manifestations: FAT RN

A useful mnemonic to remember the classic symptoms of TTP includes:

• Fever: Often observed in acute episodes; may indicate an underlying inflammatory process.

• Anemia: Patients experience microangiopathic hemolytic anemia (MAHA) as red blood cells are damaged passing through obstructed vessels.

• Thrombocytopenia: Low platelet count is a hallmark finding; patients may present with easy bruising or bleeding tendencies.

• Renal Failure: Decline in kidney function due to microthrombi affecting renal vasculature; may present as oliguria or elevated creatinine levels.

• Neurological Changes: Such as headache, confusion, focal neurological deficits, stroke, or seizure, which may indicate cerebral involvement due to thrombi.

Anemia Details

• In TTP, the mechanism of microangiopathic hemolytic anemia results from the mechanical destruction of red blood cells as they traverse occluded microvessels laden with thrombi.

• Schistocytes: Fragmented red blood cells often seen on peripheral blood smear; their presence suggests significant vascular pathology and assists in the diagnosis of TTP.

Thrombocytopenia Mechanism

• In TTP, thrombocytopenia primarily occurs because platelets become trapped in excessive vWF, rather than circulating freely. This leads to clinical manifestations such as petechiae and purpura, indicative of bleeding under the skin due to low platelet availability.

Diagnosis

Laboratory Findings:

• Severely low platelet levels (typically under 30,000 platelets per microliter).

• Normal Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) in coagulation panels, helping to distinguish TTP from other clotting disorders such as Disseminated Intravascular Coagulation (DIC).

• Identification of schistocytes on blood smear, hinting at associated hemolytic processes.

• A decrease in ADAMTS-13 activity can be confirmed with specialized assays, although immediate diagnosis and treatment are imperative and should not await these results due to the clinical urgency.

Treatment Strategies

Plasma Exchange (Plasmapheresis):

• This is the first-line treatment for TTP, where the patient's plasma, containing harmful autoantibodies against ADAMTS-13, is removed and replaced with healthy donor plasma.

• Plasma exchange enables the restoration of functional ADAMTS-13, effectively reducing vWF levels and reversing thrombotic manifestations.

Importance of Prompt Treatment:

• TTP is a life-threatening emergency, and early intervention with plasma exchange is critical to improve patient survival and outcomes. Historically, mortality rates for untreated TTP were as high as 90%, demonstrating the significance of immediate care and management as part of the standard treatment protocol for TTP.