Acquired/immune-mediated thrombotic thrombocytopenic purpura (aTTP/iTTP) is a rare, rapidly progressing, life-threatening medical emergency. It has been reported in literature that, when left untreated, death may occur in up to 90% of patients with aTTP/iTTP, making urgent diagnosis and treatment a necessity.^1-6

Complex presentation of TTP often causes a delay in diagnosis⁷

TTP presents with highly variable, multiorgan symptoms that resemble a series of thrombotic microangiopathy (TMAs) and other disorders. It is therefore critical to differentiate TTP from other similarly presenting conditions. The table below compares TTP with other resembling conditions.

Clinical picture of TTP, HUS, and DIC^8-15

	TTP	HUS	DIC
Presenting symptoms	Thrombocytopenia (platelet count <150 × 10⁹/L or >25% reduction from baseline)^8,9 MAHA (presence of schistocytes)^8,9 Organ ischemia^8,9
Types	Congenital and acquired/immune-mediated TTP (cTTP and aTTP/iTTP)^10,11	Infection-associated or atypical/complement-mediated HUS (IA-HUS or aHUS/CM-HUS)^11,12	Overt and nonovert DIC¹³
Age	cTTP—usually children¹¹ aTTP/iTTP—usually adults¹¹	IA-HUS—common in children¹⁴ aHUS/CM-HUS—any age¹⁴	NA
Cause	cTTP—inherited mutations of ADAMTS13¹¹ aTTP/iTTP—autoantibodies against ADAMTS13¹¹	IA-HUS—toxins produced by certain bacteria^14,15 aHUS/CM-HUS—activation of the complement system^14,15	Occurs as a result of underlying diseases such as sepsis, malignancy, trauma, liver diseases, obstetric disorders, envenomation, vascular anomalies, and major transfusion reactions¹³
Potential laboratory results	Platelet count <30 × 10⁹/L¹⁵ Creatinine <2.25 mg/dL¹⁵ PT and aPTT—normal⁸ D-dimer—normal⁸ ADAMTS13 <10%¹⁵	Platelet count <30 × 10⁹/L¹⁵ Creatinine >2.25 mg/dL¹⁵ PT and aPTT—normal⁸ D-dimer—normal⁸ ADAMTS13 ≥10%¹⁵	Platelet count <50 × 10⁹/L¹⁴ PT and aPTT—prolonged^13,14 D-dimer—elevated^13,14
Test(s) conﬁrming the diagnosis	cTTP—ADAMTS13 sequencing^11,15 aTTP/iTTP—ADAMTS13 testing^11,15	IA-HUS—culture test, PCR, ADAMTS13 testing^8,14 aHUS/CM-HUS—culture test, ADAMTS13 testing^8,14	ISTH scoring system for overt DIC¹³

Severe thrombocytopenia, MAHA, and organ ischemia indicate aTTP/iTTP is likely—ADAMTS13 activity <10% confirms a diagnosis¹⁰

See what Guidelines suggest about treating as soon as you suspect aTTP/iTTP.

There are 2 types of TTP: aTTP/iTTP and cTTP. aTTP/iTTP is caused by autoantibody inhibition of ADAMTS13 activity, whereas cTTP is caused by mutations in the ADAMTS13 gene. The following chart describes an algorithm to help distinguish aTTP/iTTP from cTTP.

Flowchart to differentiate aTTP/iTTP from cTTP after TTP diagnosis

CABLIVI is not indicated for congenital TTP.

Adapted from: Kremer Hovinga JA et al. Nat Rev Dis Primers. 2017;3:17020.

EHR capabilities such as Rule Messages can support proactive identification of at-risk patients for further evaluation to differentiate aTTP/iTTP from other conditions

DOWNLOAD THE EHR GUIDE

CABLIVI^® (caplacizumab-yhdp) presents similarly to other TMAs

DIFFERENTIATE aTTP/iTTP

ISTH Guideline recommendations*

SEE THE RECOMMENDATIONS

*A conditional recommendation defined as desirable effects of the recommendation probably outweighing the undesirable effects. Assumes timely access to ADAMTS13 testing and clinical diagnosis based on high likelihood of aTTP/iTTP. In de novo patients where no reasonable access to ADAMTS13 activity testing is available, the Guidelines do not recommend CABLIVI; however, treatment of a patient previously diagnosed with aTTP/iTTP could be safely undertaken on clinical grounds without the need for a confirmatory ADAMTS13 test.¹⁶

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 13; aPTT=activated partial thromboplastin time; DIC=disseminated intravascular coagulation; EHR=electronic health record; HUS=hemolytic uremic syndrome; IgG=immunoglobulin G; ISTH=International Society on Thrombosis and Haemostasis; MAHA=microangiopathic hemolytic anemia; PCR=polymerase chain reaction; PT=prothrombin time; TMA=thrombotic microangiopathy; TTP=thrombotic thrombocytopenic purpura.

INDICATIONS

CABLIVI (caplacizumab-yhdp) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients. Hypersensitivity reactions have included urticaria.

WARNINGS AND PRECAUTIONS:

Hemorrhage:

CABLIVI increases the risk of bleeding. In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of subjects. Overall, bleeding events occurred in approximately 58% of patients on CABLIVI versus 43% of patients on placebo.
In the postmarketing setting cases of life-threatening and fatal bleeding were reported in patients receiving CABLIVI.
The risk of bleeding is increased in patients with underlying coagulopathies (e.g. hemophilia, other coagulation factor deficiencies). It is also increased with concomitant use of CABLIVI with drugs affecting hemostasis and coagulation.
Avoid concomitant use of CABLIVI with antiplatelet agents or anticoagulants. If clinically significant bleeding occurs, interrupt use of CABLIVI. Von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If CABLIVI is restarted, monitor closely for signs of bleeding.
Withhold CABLIVI for 7 days prior to elective surgery, dental procedures or other invasive interventions. If emergency surgery is needed, the use of von Willebrand factor concentrate may be considered to correct hemostasis. After the risk of surgical bleeding has resolved, and CABLIVI is resumed, monitor closely for signs of bleeding.

ADVERSE REACTIONS:

The most common adverse reactions (>15% of patients) were epistaxis (29%), headache (21%) and gingival bleeding (16%).

CONCOMITANT USE OF ANTICOAGULANTS OR ANTIPLATELET AGENTS:

Concomitant use of CABLIVI with any anticoagulant or antiplatelet agent may increase the risk of bleeding. Avoid concomitant use when possible. Assess and monitor closely for bleeding with concomitant use.

PREGNANCY:

There are no available data on CABLIVI use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.

Fetal/neonatal adverse reactions: CABLIVI may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.
Maternal adverse reactions: All patients receiving CABLIVI, including pregnant women, are at risk for bleeding. Pregnant women receiving CABLIVI should be carefully monitored for evidence of excessive bleeding.

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INDICATIONS

IMPORTANT SAFETY INFORMATION

References: 1. Scully M, Hunt BJ, Benjamin S, et al; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-335. doi:10.1111/j.1365-2141.2012.09167.x 2. Goel R, King KE, Takemoto CM, Ness PM, Tobian AAR. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: nationally representative data from 2007 to 2012. Transfusion. 2016;56(6):1451-1458. doi:10.1111/trf.13586 3. Grall M, Azoulay E, Galicier L, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: causes of diagnostic errors and consequence on outcome. Experience of the French Thrombotic Microangiopathies Reference Centre. Am J Hematol. 2017;92(4):381-387. doi:10.1002/ajh.24665 4. Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500-1511. doi:10.1182/blood-2009-09-243790 5. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017;15(7):1448-1452. doi:10.1111/jth.13716 6. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015;125(25):3860-3867. doi:10.1182/blood-2014-11-551580 7. Gallan AJ, Chang A. A new paradigm for renal thrombotic microangiopathy. Semin Diagn Pathol. 2020;37(3):121-126. doi:10.1053/j.semdp.2020.01.002 8. Vincent J-L, Castro P, Hunt BJ, et al. Thrombocytopenia in the ICU: disseminated intravascular coagulation and thrombotic microangiopathies—what intensivists need to know. Crit Care. 2018;22(1):158. doi:10.1186/s13054-018-2073-2 9. Nguyen TC, Cruz MA, Carcillo JA. Thrombocytopenia-associated multiple organ failure and acute kidney injury. Crit Care Clin. 2015;31(4):661-674. doi:10.1016/j.ccc.2015.06.004 10. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. doi:10.1182/blood-2016-10-709857 11. Chiasakul T, Cuker A. Clinical and laboratory diagnosis of TTP: an integrated approach. Hematology Am Soc Hematol Educ Program. 2018;2018(1):530-538. doi:10.1182/asheducation-2018.1.530 12. Wada H, Matsumoto T, Suzuki K, et al. Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy. Throm J. 2018;16:14. doi:10.1186/s12959-018-0168-2 13. Venugopal A. Disseminated intravascular coagulation. Indian J Anaesth. 2014;58(5):603-608. doi:10.4103/0019-5049.144666 14. Canpolat N. Hemolytic uremic syndrome. Turk Pediatri Ars. 2015;50(2):73-82. doi:10.5152/tpa.2015.2297 15. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3:17020. doi:10.1038/nrdp.2017.20 16. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2486-2495. doi:10.1111/jth.15006

Diagnosing aTTP/iTTP

Complex presentation of TTP often causes a delay in diagnosis7

Clinical picture of TTP, HUS, and DIC8-15

Severe thrombocytopenia, MAHA, and organ ischemia indicate aTTP/iTTP is likely—ADAMTS13 activity <10% confirms a diagnosis10

Confirming acquired/immune-mediated TTP vs congenital TTP after diagnosis11,15expand_more

EHR capabilities such as Rule Messages can support proactive identification of at-risk patients for further evaluation to differentiate aTTP/iTTP from other conditions

CABLIVI® (caplacizumab-yhdp) presents similarly to other TMAs

ISTH Guideline recommendations*

INDICATIONS

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS:

CONCOMITANT USE OF ANTICOAGULANTS OR ANTIPLATELET AGENTS:

PREGNANCY:

INDICATIONS

IMPORTANT SAFETY INFORMATION

Complex presentation of TTP often causes a delay in diagnosis⁷

Clinical picture of TTP, HUS, and DIC^8-15

Severe thrombocytopenia, MAHA, and organ ischemia indicate aTTP/iTTP is likely—ADAMTS13 activity <10% confirms a diagnosis¹⁰

CABLIVI^® (caplacizumab-yhdp) presents similarly to other TMAs