Occlusive vasculopathy

Occlusive vasculopathy
Photo of a leg affected by livedoid vasculopathy, a type of occlusive vasculopathy.
Pronunciation
  • /əˈkluːsɪv væskjəˈlɒpəθi/
SymptomsRetiform purpura, skin lesions, nodules, ulcerations, necrosis, livedo racemosa
TypesVascular coagulopathy, systemic coagulopathy, platelet plugging, cold-related agglutination, embolization, and others
TreatmentWound control, antithrombotic therapy, etc.

Occlusive vasculopathy (from Latin vāsculum "vasculo-", meaning "vessel", and Ancient Greek πάθεια "-pathy", meaning "disorder of") is a group of vascular disorders with a blockage in one or more blood vessels caused by excessive clotting of blood. A broad range of underlying causes are found, hypercoagulability for example . The main symptoms of these disorders are primarily retiform purpura, which are branching purple patches on the skin resulting from obstructed blood flow and oxygen supply, skin lesions, nodules, ulcerations, cell death (necrosis), and livedo racemosa, which is a purple net-like pattern of discoloration.

While there is no single recognised classification system for occlusive vasculopathy, recent research does so by its different underlying causes. A diagnosis of occlusive vasculopathy can be confirmed via skin biopsy, and is treated by removing the blockage using specific methods that address the root cause of each case and wound management. Historically, occlusive vasculopathy has frequently been confused with vasculitis, where inflammation damages blood vessels (occlusive vasculopathy is non-inflammatory), causing misdiagnoses and wrongful treatment.

Classification

Currently, there is no one unified way to classify the different occlusive vasculopathy disorders due to differing classification principles, failure to distinguish between vasculitis and vasculopathy, as well as difficulty in comparing organ-specific features in systemic cases.[1] There have been attempts to algorithmically classify the disorders by 1) differentiating vasculopathies affecting small- versus medium-sized blood vessels 2) categorizing subtypes within small- and medium-sized blood vessel vasculopathies respectively 3) further categorizing by looking at the life cycles of the vasculopathies.[1][2]

An alternative way of classification does so using their various underlying causes (etiology), grouping them into the categories: vascular coagulopathy, systemic coagulopathy, platelet plugging, cold-related agglutination, embolization, and others.[3]

Diagram of occlusive vasculopathy classification by etiology.

Vascular coagulopathy

Compared to systemic coagulopathy, vascular coagulopathy is more localized.[3]

  • Sneddon syndrome describes an idiopathic livedo reticularis (similar to the previously described racemosa) or livedo racemosa with recurring lesions on the nervous and vascular systems due to blockages in small and medium sized arteries mainly in young women.[3]
  • Livedoid vasculopathy is a chronic and painful blood clot blockage caused by interplay of various dysfunctions in coagulation that mainly affects the lower limbs.[3][4]
  • Atrophic papulosis is a rare genetic disorder characterized by multi-organ vasculopathy. It has a systemic form and a cutaneous form which does not involve internal organs and is just characterized by skin lesions.[3]

Systemic coagulopathy

Right leg affected by warfarin-induced necrosis

This is when there is a severe, widespread disruption of blood clotting mechanisms in the body,[3] and can be a result of:

Platelet plugging

Platelets are an important component in blood clotting, as they adhere to damaged blood vessel surfaces to form a plug to seal off injuries,[6] so dysfunction in platelet activity can be a cause for excessive clotting.[3]

Figure of antibodies causing agglutination in cold temperatures

Rarely, certain antibodies cause agglutination (clumping), in cold temperatures[8] and cold-related agglutination may be cause blockages and lead to vasculopathic disorders,[3] such as in:

Embolization

Besides blood clots, other foreign bodies called emboli can cause blockages in vessels, such as:

Others

Other causes for occlusive vasculopathy not covered by the previous categories, such as:

Signs and symptoms

While each subtype of occlusive vasculopathy has its own set of symptoms, it is mainly characterized by retiform purpura, which are branching patches of purplish discoloration caused by bleeding into the skin due to cell death caused by blockage of the blood vessels and oxygen supply.[12] Other common symptoms include skin lesions, nodules, ulcerations, cell death (necrosis), and livedo racemosa, which is a net-like pattern of purplish discoloration with patchy, broken rings due to blockage of blood vessels but without resulting cell death like in purpura.[12][13]

Mechanism

Occlusive vasculopathy often starts with excessive blood coagulation ability, which increases the risk of forming a blood clot (thrombus) that blocks the blood vessel. Blockage can also be caused by other obstruction (embolus), such as detatched blood clots from other sites of the body, cholesterol plaques, malignant cells, oxalate crystals, etc.[3][14]

The development of occlusive vasculopathy can be divided into 4 stages.

Diagram depicting the development of occlusive vasculopathy.

Thrombotic event

In the early stage, a blood clot begins forming inside the blood vessel, starting from a fibrin thrombus. The blockage induces leakage of blood vessels (hemorrhage), and shortage of oxygen and nutrients to tissues (ischemia). At this stage, the disorder presents as retiform purpura, the net-like purple patches on the skin, typical of occlusive vasculopathy.[15]

Necrosis

Disease progression is marked by patches of dying tissue from prolonged starvation of oxygen and nutrients, forming extremely painful necrotic lesions. During this stage, immune cells like neutrophils, lymphocytes, and macrophages enter the wound site.[15]

Lymphocytic vascular reorganization

As the blood clot breaks down, a subtype of immune cell called lymphocytes forms a ring surrounding the obstructed blood vessel. Alternative names for this phase include "secondary vasculitis", or "secondary inflammatory response".[15]

Recovery

At last, the blood vessel is rebuilt into a functional blood vessel by recanalisation. If the damage is irreversible, fibroblasts travel to the wound site and deposit collagen, healing as white scars named atrophie blanche.[15]

Diagnosis

Diagnosis typically begins with a clinical assessment, followed by laboratory tests and skin biopsy to confirm.

Laboratory tests

Initial diagnosis includes blood tests that support the diagnosis of occlusive vasculopathy.[16]

Tissue biopsy

Diagram showing procedures of a skin punch biopsy.

Since blood tests alone are insufficient to confirm the diagnosis, a skin biopsy often follows. A small skin sample is taken from the wound's border, at the junction between healthy skin and the lesion.[20][21]

Typical observations include:[16]

  • Visible blockage within the affected blood vessel, such as a blood clot
  • Red blood cells that leaked out of the damaged blood vessel from hemorrhage
  • A ring of lymphocytes surrounding the blood vessel

With the help of immunohistochemistry techniques, the tissue sample can sometimes reveal subtypes of occlusive vasculopathy. For example:[16]

Treatment

A staircase model is used in treating occlusive vasculopathy, working up from addressing immediate symptoms to resolving the root cause through a stepped-care treatment plan.[21]

Treatment for occlusive vasculopathy, administered in a staircase model.

Wound management

Treatment starts with basic measures to manage ulcers, decrease pain, and improve blood circulation. For example, compression stockings to encourage blood or tissue fluids to return back to the heart (addressing venous insufficiency and edema), and topical perfusion-promoting medications to be applied on the wound (addressing lack of blood flow). Removing risk factors that set back the wound healing process, such as smoking or drastic changes in temperature, is used in some cases.[20]

Antithrombotic therapy

Many cases of occlusive vasculopathy are caused by blood clots. Hence, antithrombotic agents are commonly administered to remove the blockage. Anticoagulants target proteins in the blood coagulation cascade to slow blood clotting (e.g. rivaroxaban, enoxaparin, or warfarin). While antiplatelets prevent platelet cells from clumping to form blood clots (e.g. aspirin, pentoxifylline, or dipyridamole).[23]

Addressing refractory cases

If therapies fail to control progression of the disease, additional treatments are administered to accelerate wound healing. This includes psoralen and UV-A photochemotherapy that reduces the size of lesion,[24] hyperbaric oxygen therapy to help oxygen reach the wound site,[25] and anti-inflammatory drugs (e.g. colchicine, dapsone, or hydroxychloroquine).[20] Medication that restores circulation are also used. Including fibrinolytics to break down the thrombi (e.g. tPA),[26] and vasodilators to facilitate the primary antithrombotic therapies (e.g. nifedipine).[20]

Currently, a few emerging therapies are aimed at rectifying the damage. For example intravenous immunoglobulin therapy, JAK inhibitors (e.g. baricitinib), and TNF inhibitors (e.g. etanercept). Yet, these drugs are not adapted as the standard treatment, as its effects are only proven by initial results from pilot studies.[20]

Addressing non-thrombotic embolus

When the obstruction is formed by substances other than blood clots, a different set of treatment method is applied:

Cholesterol embolism is commonly treated in three stages. First by stabilising the cholesterol blockage with low-molecular-weight heparin, then administering iloprost to widen the blood vessels, and finally alleviating the lymphocyte responses using corticosteroids or colchicine.[13]

Heparin necrosis is generally resolved by discontinuing heparin treatment, and replacing it with other anticoagulation agents (e.g. argatroban, danaparoid, bivalirudin, or fondaparinux).[13]

Microorganism-associated embolism is treated with antimicrobial therapies tailored specific to the infection.[15]

History

Historically, occlusive vasculopathy (with a non-inflammatory cause) is often confused with vasculitis (caused by blood vessels actively attacked by inflammatory cells).[27] The two diseases can present with similar symptoms in the initial clinical assessment. Therefore, affected individuals were often misdiagnosed with vasculitis and treated with high-dose corticosteroids or immunosuppressive agents,[28] which brings impactful side effects.[29] In addition, older literature may mix up the mechanism, prognosis, and therapy between the two disorders, leading to conflicting recommendations.[30][31]

Though the difference between occlusive vasculopathy and vasculitis is repeatedly emphasised, these two disorders can occur at the same time. Vasculitis can trigger blood-vessel-blocking events (e.g. in septic vasculitis), and vice versa, occluding vasculopathies may mimic vasculitis (e.g. in lymphocytic vascular reorganization).[15]

See also

References

  1. 1 2 Ratzinger, Gudrun; Zelger, Bettina G.; Zelger, Bernhard W. (2019-09-05). "Bar code reader - an algorithmic approach to cutaneous occluding vasculopathies? Part I: small vessel vasculopathies". Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology: JDDG. 17 (9): 895–904. doi:10.1111/ddg.13930. ISSN 1610-0387. PMC 6851626. PMID 31487114.
  2. ↑ Wilk, Michael; Zelger, Bettina G.; Zelger, Bernhard (2023-02-01). "Vasculitides and occluding vasculopathies, challenges in recognizing histopathological patterns, and their solutions". Frontiers in Medicine. 9 994450. doi:10.3389/fmed.2022.994450. ISSN 2296-858X. PMC 9929945. PMID 36816722.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Park, Joonsoo; Hoang, Mai P. (2020), "Vasculopathy", in Hoang, Mai P.; Selim, Maria Angelica (eds.), Hospital-Based Dermatopathology: An Illustrated Diagnostic Guide, Cham: Springer International Publishing, pp. 297–347, doi:10.1007/978-3-030-35820-4_8, ISBN 978-3-030-35820-4
  4. ↑ Majmundar, Vidit D.; Syed, Hasnain A.; Baxi, Kalgi (2026), "Livedoid Vasculopathy", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32644463, retrieved 2026-04-13
  5. ↑ Costello, Ryan A.; Leslie, Stephen W.; Nehring, Sara M. (2026), "Disseminated Intravascular Coagulation", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 28722864, retrieved 2026-04-13
  6. ↑ Periayah, Mercy Halleluyah; Halim, Ahmad Sukari; Mat Saad, Arman Zaharil (2017-10-01). "Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis". International Journal of Hematology-Oncology and Stem Cell Research. 11 (4): 319–327. ISSN 2008-3009. PMC 5767294. PMID 29340130.
  7. ↑ Sukumar, Senthil; Lämmle, Bernhard; Cataland, Spero R. (2021-02-02). "Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management". Journal of Clinical Medicine. 10 (3): 536. doi:10.3390/jcm10030536. ISSN 2077-0383. PMC 7867179. PMID 33540569.
  8. ↑ Gabbard, Amy P.; Booth, Garrett S. (2020-07-17). "Cold Agglutinin Disease". Clinical Hematology International. 2 (3): 95–100. doi:10.2991/chi.k.200706.001. ISSN 2590-0048. PMC 8432332. PMID 34595449.
  9. ↑ Della Mura, Mario; Sorino, Joana; Angiuli, Filippo Emanuele; Cazzato, Gerardo; Gaudio, Francesco; Ingravallo, Giuseppe (2025-07-15). "Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease". Cancers. 17 (14): 2355. doi:10.3390/cancers17142355. ISSN 2072-6694. PMC 12293582. PMID 40723240.
  10. ↑ El-Saygeh, Skye; Roese, Douglas; Moe, Sharon M. (2020-01-18). "Calciphylaxis or vascular oxalosis?". Clinical Kidney Journal. 14 (1): 435–438. doi:10.1093/ckj/sfz190. ISSN 2048-8505. PMC 7857799. PMID 33564451.
  11. ↑ Lee, Kachiu C.; Ladizinski, Barry; Federman, Daniel G. (2012-06-01). "Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge". Mayo Clinic Proceedings. 87 (6): 581–586. doi:10.1016/j.mayocp.2012.03.010. ISSN 1942-5546. PMC 3498128. PMID 22677078.
  12. 1 2 Eswaran, Harish; Googe, Paul; Vedak, Priyanka; Marston, William A.; Moll, Stephan (2020-02-29). "Livedoid vasculopathy: A review with focus on terminology and pathogenesis". Vascular Medicine (London, England). 27 (6): 593–603. doi:10.1177/1358863X221130380. ISSN 1477-0377. PMC 9732787. PMID 36285834.
  13. 1 2 3 Burg, Maria Rosa; Hansen, Inga; Torster, Leopold Konstantin; Schneider, Stefan Werner (2025-04-04). "Occlusive cutaneous vasculopathies: rare differential diagnoses". JDDG: Journal der Deutschen Dermatologischen Gesellschaft (in German). 23 (4): 487–506. doi:10.1111/ddg.15543. ISSN 1610-0379. PMID 40183741.
  14. ↑ Ronicke, Moritz; Berking, Carola; Erfurt-Berge, Cornelia (2024-02-20). "Occlusive cutaneous vasculopathies as cause of chronic ulcers". JDDG: Journal der Deutschen Dermatologischen Gesellschaft (in German). 22 (4): 553–567. doi:10.1111/ddg.15276. ISSN 1610-0379. PMID 38379266.
  15. 1 2 3 4 5 6 Wilk, Michael; Zelger, Bettina G.; Zelger, Bernhard (2023-02-01). "Vasculitides and occluding vasculopathies, challenges in recognizing histopathological patterns, and their solutions". Frontiers in Medicine. 9 994450. doi:10.3389/fmed.2022.994450. ISSN 2296-858X. PMC 9929945. PMID 36816722.
  16. 1 2 3 Llamas-Velasco, Mar; Alegría, Victoria; Santos-Briz, Ángel; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis (2017-09-28). "Occlusive Nonvasculitic Vasculopathy". The American Journal of Dermatopathology. 39 (9): 637–662. doi:10.1097/DAD.0000000000000766. ISSN 0193-1091. PMID 27759698.
  17. ↑ Seo, In-Ho; Lee, Yong-Jae (2022-10-25). "Usefulness of Complete Blood Count (CBC) to Assess Cardiovascular and Metabolic Diseases in Clinical Settings: A Comprehensive Literature Review". Biomedicines. 10 (11): 2697. doi:10.3390/biomedicines10112697. ISSN 2227-9059. PMC 9687310. PMID 36359216.
  18. ↑ Rasmussen, Katrine Laura; Philips, Malou; Tripodi, Armando; Goetze, Jens Peter (2020-02-12). "Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini-review". European Journal of Haematology. 104 (6): 519–525. doi:10.1111/ejh.13394. ISSN 0902-4441. PMID 32049377.
  19. ↑ Weiner, Maria; Segelmark, Mårten (2016-07-29). "The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA)". Autoimmunity Reviews. 15 (10): 978–982. doi:10.1016/j.autrev.2016.07.016. PMID 27481040.
  20. 1 2 3 4 5 Seguí, Mireia; Llamas-Velasco, Mar (2022-12-08). "A comprehensive review on pathogenesis, associations, clinical findings, and treatment of livedoid vasculopathy". Frontiers in Medicine. 9 993515. doi:10.3389/fmed.2022.993515. ISSN 2296-858X. PMC 9773082. PMID 36569162.
  21. 1 2 Hadir, Shakshouk; Alexander, Hines; Shannon, Kody; Nicole, Fett; Afsaneh, Alavi; Alex, G. Ortega-Loayza (2024-12-01). Inflammatory and vaso-occlusive ulcers: Part I - Clinical presentation and diagnosis. Vol. 91.6. Journal of the American Academy of Dermatology. pp. 1035–1048. Retrieved 2026-04-01.
  22. ↑ Knight, Jason S.; Kanthi, Yogendra (2022-05-01). "Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome". Seminars in Immunopathology. 44 (3): 347–362. doi:10.1007/s00281-022-00916-w. ISSN 1863-2300. PMC 8816310. PMID 35122116.
  23. ↑ Heestermans, Marco; Poenou, Géraldine; Hamzeh-Cognasse, Hind; Cognasse, Fabrice; Bertoletti, Laurent (2022-10-13). "Anticoagulants: A Short History, Their Mechanism of Action, Pharmacology, and Indications". Cells. 11 (20): 3214. doi:10.3390/cells11203214. ISSN 2073-4409. PMC 9600347. PMID 36291080.
  24. ↑ Breuckmann, Frank; Gambichler, Thilo; Altmeyer, Peter; Kreuter, Alexander (2004-09-20). "UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review". BMC Dermatology. 4 (1): 11. doi:10.1186/1471-5945-4-11. ISSN 1471-5945. PMC 521488. PMID 15380024.
  25. ↑ Ortega, Miguel A.; Fraile-Martinez, Oscar; García-Montero, Cielo; Callejón-Peláez, Enrique; Sáez, Miguel A.; Álvarez-Mon, Miguel A.; García-Honduvilla, Natalio; Monserrat, Jorge; Álvarez-Mon, Melchor; Bujan, Julia; Canals, María Luisa (2021-08-24). "A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities". Medicina. 57 (9): 864. Bibcode:2021Medi...57..864O. doi:10.3390/medicina57090864. ISSN 1648-9144. PMC 8465921. PMID 34577787.
  26. ↑ Hvas, Christine Lodberg; Larsen, Julie Brogaard (2023-09-16). "The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment". International Journal of Molecular Sciences. 24 (18) 14179. doi:10.3390/ijms241814179. ISSN 1422-0067. PMC 10532028. PMID 37762481.
  27. ↑ Ecclestone, Tegwen; Watts, Richard A. (2023-03-01). "Classification and epidemiology of vasculitis: Emerging concepts". Best Practice & Research Clinical Rheumatology. PART A - Practical Procedures 'How to do' & PART B - Vasculitis. 37 (1) 101845. doi:10.1016/j.berh.2023.101845. ISSN 1521-6942. PMID 37468418.
  28. ↑ Eleftheriou, Despina; Brogan, Paul A. (2016-04-26). "Therapeutic advances in the treatment of vasculitis". Pediatric Rheumatology. 14 (1): 26. doi:10.1186/s12969-016-0082-8. ISSN 1546-0096. PMC 4845429. PMID 27112923.
  29. ↑ Hussain, Yaseen; Khan, Haroon (2022), "Immunosuppressive Drugs", Encyclopedia of Infection and Immunity, Elsevier, pp. 726–740, doi:10.1016/B978-0-12-818731-9.00068-9, ISBN 978-0-323-90303-5, PMC 8987166
  30. ↑ Suresh, E (2006-08-01). "Diagnostic approach to patients with suspected vasculitis". Postgraduate Medical Journal. 82 (970): 483–488. doi:10.1136/pgmj.2005.042648. ISSN 0032-5473. PMC 2585712. PMID 16891436.
  31. ↑ Bilgic, Asli; Ozcobanoglu, Salih; Bozca, Burcin Cansu; Alpsoy, Erkan (2021-12-01). "Livedoid vasculopathy: A multidisciplinary clinical approach to diagnosis and management". International Journal of Women's Dermatology. House of Medicine and Dermatology. 7 (5, Part A): 588–599. doi:10.1016/j.ijwd.2021.08.013. ISSN 2352-6475. PMC 8721056. PMID 35024414.
This page is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.