Rash with fever resident survival guide: Difference between revisions
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gonococcal infection|j09=[[Rocky Mountain spotted fever]]|u09=[[Meningococcemia]]}} | gonococcal infection|j09=[[Rocky Mountain spotted fever]]|u09=[[Meningococcemia]]}} | ||
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{{Family tree | |p09| | |c09| |s09| |u09| |q09| | | | | |q09=<div style="float: left; text-align: left; height: 24em; width: 12em; padding:1em;"> '''Treatment:'''<br> | {{Family tree | |p09| | |c09| |s09| |u09| |q09| | |a01| |b01| | |c01| |a01=<div style="float: left; text-align: left; height: 56em; width: 12em; padding:1em;"> '''Treatment:'''<ref name="pmid19222477">{{cite journal |vauthors=Levi M, Toh CH, Thachil J, Watson HG |title=Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology |journal=Br. J. Haematol. |volume=145 |issue=1 |pages=24–33 |date=April 2009 |pmid=19222477 |doi=10.1111/j.1365-2141.2009.07600.x |url= |issn=}}</ref><br> | ||
---- | |||
❑ The primary treatment of DIC is treatment of the underlying condition <br> ❑ In patients with DIC and bleeding or at high risk of bleeding and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered but non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless there is a high risk of bleeding. <br> ❑Activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful in DIC patients with prolonged prothrombin time (PT).<br/>❑In patients where FFP can not be used due to chances of fluid overload,factor concentrates can be used. <br> ❑ Patients with DIC with a primary hyperfibrinolytic state and severe bleeding can be treated with lysine analogues, such as tranexamic acid, 1 g every 8 hourly is administered. </div> |q09=<div style="float: left; text-align: left; height: 24em; width: 12em; padding:1em;"> '''Treatment:'''<br> | |||
---- | ---- | ||
❑❑ [[Ceftriaxone]] is first-line therapy. [[Vancomycin]] should be added <br> ❑[[Rifampin]] is used as prophylaxis in close contacts of the patients,alternatively single-dose [[ciprofloxacin]] and IM [[ceftriaxone]] can be administered<br/>❑ [[Dexamethasone]] can reduce neurologic sequelae if given early,even before administering antibiotics<br/> </div> <br> |u09=<div style="float: left; text-align: left; height: 24em; width: 12em; padding:1em;"> '''Treatment:'''<br> | ❑❑ [[Ceftriaxone]] is first-line therapy. [[Vancomycin]] should be added <br> ❑[[Rifampin]] is used as prophylaxis in close contacts of the patients,alternatively single-dose [[ciprofloxacin]] and IM [[ceftriaxone]] can be administered<br/>❑ [[Dexamethasone]] can reduce neurologic sequelae if given early,even before administering antibiotics<br/> </div> <br> |u09=<div style="float: left; text-align: left; height: 24em; width: 12em; padding:1em;"> '''Treatment:'''<br> |
Revision as of 07:59, 27 August 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rinky Agnes Botleroo, M.B.B.S.
Synonyms and keywords:
Overview
This section provides a short and straight to the point overview of the disease or symptom. The first sentence of the overview must contain the name of the disease.
Causes
Life Threatening Causes
Life-threatening causes of febrile rashes include conditions that may result in death or permanent disability within 24 hours if left untreated.[1]
- Meningococcemia or Meningoencephalitis
- Thrombotic Thrombocytopenic Purpura (TTP)
- Disseminated Intravascular Coagulation (DIC)
- Bacterial sepsis(Pneumococcal, Staphylococcal)
Common Causes
Common causes of rash with fever are given below :[1]
- Typhoid fever
- Dengue hemorrhagic fever
- Rocky Mountain spotted fever (RMSF)
- Scarlet fever
- Toxic Epidermal Necrolysis (TEN)
- Stevens-Johnson Syndrome (SJS)
- Henoch-Schonlein Purpura (HSP)
- Kawasaki disease
- Lyme disease
- Endocarditis
- Disseminated gonococcal infection
- Autoimmune vasculitis
- Varicella
- Necrotizing fasciitis
- Hand foot and mouth (HFM) disease
- Anaphylaxis
- Shingles
- Rubella
- Measles
Diagnosis
Shown below are 04 algorithms summarizing the diagnosis of Rash with fever in a patient:[2][1]
Patient with Fever and Rash | |||||||||||||||||||||||||
Take complete history | |||||||||||||||||||||||||
Record Vital signs: ❑ Measure the temperature | |||||||||||||||||||||||||
Ask about associated symptoms: ❑ Vomiting ❑ Nausea ❑ Abdominal Pain ❑ Cough ❑ Sore throat ❑ Chest pain ❑Arthralgias | |||||||||||||||||||||||||
Ask about other medical history: ❑ Asplenia ❑ Malignancy ❑ Collagen vascular disease ❑Any recent medications ❑Valvular heart disease ❑Chronic liver disease ❑Solid organ or bone marrow transplantation ❑Steroid use ❑Chemotherapy related immune suppression | |||||||||||||||||||||||||
Ask about recent Exposure: ❑Communal living ❑ Tick exposure ❑ Dog exposure ❑ Salt water exposure ❑ Tampon use ❑ IVDU ❑Trauma and Diabetes Mellitus ❑Exposure to sexually transmitted disease, including risk factors for infection with human immunodeficiency virus (HIV) | |||||||||||||||||||||||||
Ask about recent travel history: ❑ International Travel history | |||||||||||||||||||||||||
General Physical Examination: ❑General appearance-Is the patient toxic? or normal appearance ❑Look for new-onset heart murmur or nuchal rigidity ❑Nuchal rigidity. ❑Palpate Lymph nodes for Generalized lymphadenopathy ❑Conjunctival injection ❑Look for Nikolsky sign:Sloughing of full-thickness skin with lateral pressure ❑Look for any lesion on the back, buttocks, or perineum ❑ In diabetic patients check feet ❑Palpate abdomen for hepatosplenomegaly | |||||||||||||||||||||||||||||||||||||||||
Characterize rash | |||||||||||||||||||||||||||||||||||||||||
Maculopapular rash | Petechial/Purpuric rash | Vesiculobullous rash | Erythematous rash | ||||||||||||||||||||||||||||||||||||||
Terminolgies used to diagnose Rashes[1]
Term | Clinical Features |
---|---|
Lesion | Single,Small affected area |
Rash | An eruption on the skin; more extensive than a single lesion |
Macule | Well circumscribed area of change without elevation |
Papule | Solid raised lesion ≤1 cm |
Petechia | Small red/brown macule ≤1 cm
that does not blanche |
Purpura | Hemorrhagic area > 3 mm that does not blanch |
If a patient present with fever with maculopapular rash then follow the algorithm given below:
Fever with maculopapular rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Look at the rash and it's distribution | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Central distribution with fever | Peripheral distribution with fever | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑Viral exanthem ❑Lyme disease ❑Still disease | Look for target lesion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Present | Absent | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Stevens-Johnson Syndrome | Erythema Multiforme | Lyme disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics: ❑ Usually occurs due to drug reaction ❑Diffusely distributed target lesions including the palms and soles ❑ Mucous membrane may be involved ❑Toxic appearing patient ❑Fever | Characteristics: ❑ Usually autoimmune ❑May follow Herpes simplex, Mycoplasma, Fungal diseases or may occur due to drug exposure (sulfa drugs, anticonvulsants, antibiotics) ❑ Mucous membrane not involved in EM minor ❑In EM major significant involvement of mucous membrane ❑Nonspecific upper respiratory tract infection, moderate fever, general discomfort, cough, sore throat, vomiting, chest pain, diarrhoea may occur before the onset of rash ❑Rash may be seen in the palms, soles,face, and extensor surfaces and eye involvement in 10% | Characteristics: ❑ Usually there is a history of travelling to wooden area ❑Tick-borne illness is caused by Borrelia burgdorferi ❑A big lesion with dark red border and central clearing known as Erythema migrans ❑Migratory arthalgia ❑Atrioventricular Nodal block ❑Myalgia ❑Fever ❑Bells palsy ❑Confusion ❑Meningitis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Meningococcemia | Rocky Mountain spotted fever | Syphillis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics: ❑ Infection with Neisseria meningitidis ❑ History of living in collge dormitory/millitary/prison ❑Erythematous and maculopapular that initially begins on wrists and ankles, then spreads and becomes petechial ❑Ill appearing patient ❑ Fever | Characteristics: ❑ Caused by Rickettsia rickettsii ❑ History of travel to wooden areas, primarily in the south-Atlantic region of the United States ❑Erythematous and maculopapular that initially begins on wrists and ankles, then spreads and becomes petechial ❑Ill appearing patient, can be in shock ❑High Fever | Characteristics: ❑ Caused by Treponema pallidum ❑Secondary syphilis may appear as rough, red, or reddish brown spots on the palms of the hands and the bottoms of the feet] ❑ Non-pruritic ❑Fever | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
If patient presents with Petechial/Purpuric rash
Fever with Petechial rash/Perpuric rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Palpate the rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Palpable | Non-palpable | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Endocarditis | Henoch-Schonlein purpura | Disseminated gonococcal infection | Rocky Mountain spotted fever | Meningococcemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics:[3]
❑ History of IV drug use,Infective Endocarditis, Rheumatic fever, ❑ Mostly caused by Staphylococcus and Streptococcus ❑Look for Janeway lesions which are painless purple or brown erythematous macular lesions, usually affects the palms, soles, and fingers | Characteristics: ❑ Autoimmune systemic vasculitis that affects the legs, buttocks, and arms and kidneys. ❑Usually preceded by an infection or drug exposure. ❑ The classic triad comprises of purpura, abdominal pain, and arthritis in the knees, ankles, and elbows. ❑Pruritic ❑Nausea ❑Vomiting ❑Intussusception ❑Diarrhoea/Constipation | Characteristics: ❑ Caused by Neiserria Gonorrhoea ❑Rash maybe present in case of disseminated gonococcal infection. ❑ Affects the trunk, limbs, palms and soles, and usually spare the face, scalp and mouth. | Characteristics: ❑ Caused by Rickettsia rickettsii ❑ History of travel to wooden areas, primarily in the south-Atlantic region of the United States ❑Erythematous and maculopapular that initially begins on wrists and ankles, then spreads and becomes petechial ❑Ill appearing patient, can be in shock ❑High Fever | Characteristics: ❑ Infection with Neisseria meningitidis ❑ History of living in collge dormitory/millitary/prison ❑Erythematous and maculopapular that initially begins on wrists and ankles, then spreads and becomes petechial ❑Ill appearing patient ❑ Fever | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DIC | TTP | Purpura fulminans | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics: ❑Very ill patient ❑ ❑Complication of different serious and life-threatening diseases ❑Due to uncontrolled activation of clotting factors in the blood vessels, causing clotting of blood in the whole body ❑Bleeding in other tissues | Characteristics:[4] ❑Purplish bruises or purpura/petechiae in the mouth ❑Yellowish color of the skin and sclera ❑Fatigue ❑Tachycardia ❑ Shortness of Breath | Characteristics: ❑Very ill patient ❑H/O previous infection most commonly by meningococcal or gram-negative organisms, pregnancy, massive trauma, end-stage malignant disease, hepatic failure, snakebites, transfusion reactions, and anything else that may precipitate DICs ❑Fever ❑ Shock ❑Rapid subcutaneous hemorrhage ❑Widespread organ involvement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
If patient presents with Vesiculo-bullous Rash, follow the algoritm below:
Fever with Vesicobullous rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Look at the rash and it's distribution | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diffuse distribution with fever | Localized distribution with fever | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Varicella | Purpura fulminans | Disseminated gonococcal disease | DIC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics:[5] ❑ It is caused by varicella-zoster virus (VZV) ❑Temperature up to 102°F ❑ Rash is generalized and pruritic,usually strats fromchest, back, and face, then spreads over the entire body ❑ Rash progresses rapidly from macular to papular to vesicular lesions before crusting ❑ Malaise | Characteristics: ❑Very ill patient ❑H/O previous infection most commonly by meningococcal or gram-negative organisms, pregnancy, massive trauma, end-stage malignant disease, hepatic failure, snakebites, transfusion reactions, and anything else that may precipitate DICs ❑Fever ❑ Shock ❑Rapid subcutaneous hemorrhage ❑Widespread organ involvement | Characteristics: ❑ Caused by Neiserria Gonorrhoea ❑Rash maybe present in case of disseminated gonococcal infection. ❑ Affects the trunk, limbs, palms and soles, and usually spare the face, scalp and mouth. | Characteristics: ❑Very ill patient ❑ ❑Complication of different serious and life-threatening diseases ❑Due to uncontrolled activation of clotting factors in the blood vessels, causing clotting of blood in the whole body ❑Bleeding in other tissues | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Necrotizing fasciitis | Hand-foot-and-mouth disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics: ❑ Very sick patient, may be in septic shock ❑Rapid spread of cellulitis with purpura/blistering, genitalia may be involved ❑Affercted area may have decreased sensation | Characteristics: ❑ Mainly seen in young children, caused by enterovirus ❑Symmetrical vesicles mainly hands, feet and mouth ❑Can extend to limbs and buttocks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Patient comes with Erythematous rash, follow the algorithm below:
Fever with Erythematous rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Look for Nikolsky sign | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Present | Absent | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Staphylococcal Scalded Skin Syndrome: | Toxic Epidermal Necrolysis | Kawasaki disease | Scarlet fever | Toxic Shock Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Characteristics: ❑ Mainly seen in young children,usually less than 5 years of age. ❑Sudden onset of fever. ❑Erythema of the neck, axilla, and groin, and extreme skin tenderness ❑Mucous membrane not included ❑Shallow skin cleavage plane | Characteristics: ❑ Caused by drug reaction and most commonly associated with sulfa drugs. Other drugs include anticonvulsants, antivirals, NSAIDs, and allopurinol. ❑sudden-onset diffuse erythema with tender skin and sloughing ❑Rash starts from the face and around the eyes,then spread to whole body. ❑Massive skin sloughing in large sheets ❑ Patient is toxic ❑Myalgia ❑Mucous membrane is involved ❑Immunocompromised patients,HIV patients,patient with SLE,brain tumor are the high risk population | Characteristics: ❑ Mainly seen in young children,vasculitisdue to autoimmune or infective cause ❑Affects many systems, including the skin, mucous membranes, lymphatics, and blood vessels. ❑high fever for at least 5 days ❑Diffuse erythroderma ❑Strawberry tongue ❑Significant cervical lymphadenopathy ❑Conjunctival injection, peeling of the fingers and toes ❑Edema of the extremities | Characteristics: ❑ Strawberry tongue ❑ Tiny red macules or rough papules ❑Swollen then peeling hands ❑Evidence of streptococcal infection | Characteristics: ❑ Associated with tampon use in female,abscesses, nasal packing, surgical wounds, and postpartum conditions ❑Patient is toxic, in shock, and febrile ❑Diffuse erythematous rash that eventually leads to desquamation of the hands and feet. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Treatment
Shown below is an algorithm summarizing the treatment of rash with fever
If patient comes it maculopapular rash and fever:
Fever with maculopapular rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Stevens-Johnson Syndrome | Erythema Multiforme | Lyme disease | Meningococcemia | Rocky Mountain spotted fever | Lyme disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Treatment: ❑ Discontinuation of the offending agent ❑Optimizing fluid and electrolyte levels ❑ Admit to ICU | Treatment: ❑ Mild cases (EM minor) require only symptomatic support ❑Give analgesics, cold compresses, topical steroids ❑ Treatment of the specific cause if it is found and dermatological followup visit should be scheduled ❑In Erythema major more aggressive care is needed, start with discontinuation of the causative agent ❑Fluid and electrolyte balance, analgesics for pain ❑Clean the wounded area, Silver sulfadiazine should NOT be used ❑If oral lesions are present, soothing solution can be used ❑Steroid use may give rise to further complications than benefit ❑Dermatological and opthalmologic consultation (if eyes are involved). | Treatment: ❑ Doxycycline is the first-line treatment in nonpregnant adult patients ❑Amoxicillin can be used in children | Treatment: ❑ Ceftriaxone is first-line therapy. Vancomycin should be added ❑Rifampin is used as prophylaxis in close contacts of the patients,alternatively single-dose ciprofloxacin and IM ceftriaxone can be administered ❑ Dexamethasone can reduce neurologic sequelae if given early,even before administering antibiotics | Treatment: ❑ Doxycycline is the drug of choice in all nonpregnant patients and children. ❑ Pregnant patients can be treated with chloramphenicol | Treatment: ❑ Doxycycline is the first-line treatment in nonpregnant adult patients ❑ Children can be treated with amoxicillin. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
If patient comes with Petechial/Purpuric rash
Fever with Petechial rash/Perpuric rash | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Endocarditis | Henoch-Schonlein purpura | Disseminated gonococcal infection | Rocky Mountain spotted fever | Meningococcemia | DIC | Purpura fulminans | TTP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Treatment:
❑ Initial empiric therapy is vancomycin or ampicillin/sulbactam plus an aminoglycoside . ❑Rifampin is added in patients with prosthetic valves) ❑Valve replacement should be considered in selected patients with infectious endocarditis. ❑Antimicrobial prophylaxis before certain dental and other procedures. | Treatment: ❑ Only supportive care, ❑Some patients need hospitalization for pain control, kidney biopsy, and/or administration of immunosuppressant agents or, occasionally, IVIG | Treatment:[6] ❑ Patients with DGI should be treated for at least 1 week with IV ceftriaxone. ❑ Treatment duration should be extended in patients who do not improve adequately | Treatment: ❑ Doxycycline is the drug of choice in all nonpregnant patients and children. ❑ Pregnant patients can be treated with chloramphenicol | Treatment: ❑❑ Ceftriaxone is first-line therapy. Vancomycin should be added ❑Rifampin is used as prophylaxis in close contacts of the patients,alternatively single-dose ciprofloxacin and IM ceftriaxone can be administered ❑ Dexamethasone can reduce neurologic sequelae if given early,even before administering antibiotics | Treatment:[7] ❑ The primary treatment of DIC is treatment of the underlying condition ❑ In patients with DIC and bleeding or at high risk of bleeding and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered but non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless there is a high risk of bleeding. ❑Activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful in DIC patients with prolonged prothrombin time (PT). ❑In patients where FFP can not be used due to chances of fluid overload,factor concentrates can be used. ❑ Patients with DIC with a primary hyperfibrinolytic state and severe bleeding can be treated with lysine analogues, such as tranexamic acid, 1 g every 8 hourly is administered. | {{{b01}}} | {{{c01}}} | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Do's
- If patient started any new medication,immediately should stop taking it.
- If allergic to any known product/medication/food, stop taking it.
Don'ts
- Don’t use rubbing alcohol on skin
- Don't clean open wounds with hydrogen peroxide or bleach
- Don’t use a triple-antibiotic ointment
References
- ↑ 1.0 1.1 1.2 1.3 Kang JH (September 2015). "Febrile Illness with Skin Rashes". Infect Chemother. 47 (3): 155–66. doi:10.3947/ic.2015.47.3.155. PMC 4607768. PMID 26483989.
- ↑ Murphy-Lavoie, Heather; LeGros, Tracy (2018). "The Algorithmic Approach to the Unidentified Rash": 1–5. doi:10.1007/978-3-319-75623-3_1.
- ↑ Gomes, Rafael Tomaz; Tiberto, Larissa Rezende; Bello, Viviane Nardin Monte; Lima, Margarete Aparecida Jacometo; Nai, Gisele Alborghetti; Abreu, Marilda Aparecida Milanez Morgado de (2016). "Dermatologic manifestations of infective endocarditis". Anais Brasileiros de Dermatologia. 91 (5 suppl 1): 92–94. doi:10.1590/abd1806-4841.20164718. ISSN 0365-0596.
- ↑ "Thrombotic Thrombocytopenic Purpura | NHLBI, NIH".
- ↑ "Chickenpox | For Healthcare Professionals | Varicella | CDC".
- ↑ Lohani S, Nazir S, Tachamo N, Patel N (2016). "Disseminated gonococcal infection: an unusual presentation". J Community Hosp Intern Med Perspect. 6 (3): 31841. doi:10.3402/jchimp.v6.31841. PMC 4942509. PMID 27406461.
- ↑ Levi M, Toh CH, Thachil J, Watson HG (April 2009). "Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology". Br. J. Haematol. 145 (1): 24–33. doi:10.1111/j.1365-2141.2009.07600.x. PMID 19222477.