"Unveiling Thrombotic and Thrombocytopenic Purpura: Pathogenesis, Clinical Features, and Treatment Strategies"

Thrombotic and Thrombocytopenic Purpura

Definition: TTP occurs in familial or acquired forms.

Pathogenesis: Deficiency of ADAMTS13 metalloprotease leads to ULVWF multimers.

Causes: Familial forms involve ADAMTS13 mutations;

Acquired forms result from inhibitory IgG autoantibodies.

Clinical Features: Pentad of symptoms: thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal failure, fever.

Treatment: Plasma exchange with FFP or cry supernatant, rituximab, alacizumab, and immunosuppressive therapies.

TTP is type of Thrombocytopenia mean platelets count decrease its normal count.

TTP is rare blood disorder characterized by clotting in small blood vessels (Thromboses) but unnecessary clot resulting in a low platelet count.

Normally clotting present in tissue & vessels injury.

In TTP, Patient have defect in (ADAMTS13) enzyme. ( For clearing the VWF multimers)

Normally

Gene to code for different protein.

ADAMTS13 gene its code for ADAMTS13 enzyme.

· Function of ADAMTS13 enzyme

Cleavage of ultra-large VWF multimers into VWF monomers.

VWF multimer VWF monomer

(more active) (less active)

Function of VWF

VWF secret it the time of injury.

Platelet stick together and adhere to the walls of blood vessels at the site of wound.

Platelets stick forms temporary clots, plugging holes in blood vessels walls to stop bleeding.

In case of TTP

In TTP defect is in the ADAMTS13 enzyme.

No cleavage of ultra large VWF multimers.

VWF multimers increase

VWF monomers decrease

Two Types of TTP

1) Inherited

Inherited TTP is rare.

IT is a genetic disease called up show Schulman syndrome.

Deficiency of ADAMTS13 gene deficiency of ADAMTS13 enzyme.

2) Acquired

This is common.

An inhibitor of this ADAMTS13 enzyme is present within the patient .

Nature of inhibitor of ADAMTS13 IgG Antibody against it.

1)Primary haemostasias

TTP is a problem associated with primary haemostasias.

PLT count (PC) decrease

Bleeding Time increase

2)Secondary haemostasias

No effect of secondary haemostasias

PT (prothrombin time) Normal

APTT Normal

• Clinical Features: Pentad of symptoms:

Thrombocytopenia,

Microangiopathic hemolytic anemia,

Neurological abnormalities,

Renal failure,

Fever

TTP: Pathogenesis

Deficiency of ADAMTS13 leads to inability to break down ULVWF multimers.

ULVWF multimers bind platelets, causing thrombosis.

TTP: Clinical Features

Thrombocytopenia: <150,000 platelets/μL.

Microangiopathic Hemolytic Anemia: Presence of schistocytes.

Neurological Abnormalities: Confusion, seizures, focal shortages.

TTP: Diagnosis

Bilirubin Increase

Bleeding Time Increase

HCT Decrease

RBC Decrease

Hb Decrease

PLT Count Decrease

MCV Normal

PT Normal

APTT Normal

Peripheral smear Schistocytes ( Half RBC’s)

ADAMTS13 activity test

Not only platelet disruption take place in TTP but only RBCs are effected.

TTP patients suffer from anemia also ( Normocytic)

RBC,s get ruptured when passed through the thrombi vessels therefore anemia develops and fragments which formed in these vessels are known as schistocytes.

In these patients schistocytes present in blood.

Normal RBC,s shape change.

TTP: Treatment

Plasma exchange therapy: Removes ULVWF multimers and autoantibodies.

Immunosuppressive therapy: Steroids, rituximab.

References

Hoffbrand’s Essential Haematology, Eighth Edition. By A. Victor Hoffbrand and David P. Steensma. © 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd. Companion website: www.wileyessential.com/haematology

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