Haematological emergencies in the ICU

Contents

Overview

Haematological emergencies in the ICU share common clinical features — thrombocytopenia, haemolysis, and coagulopathy — but require distinct management approaches. Misidentification leads to inappropriate treatment and worsened outcomes. A systematic approach to differentiating these conditions based on mechanism, laboratory findings, and clinical context is essential.

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is a syndrome of systemic coagulation activation leading to consumption of clotting factors and platelets. Microvascular thrombosis occurs simultaneously with haemorrhage from factor depletion.

Aetiology

DIC is not a primary diagnosis but a consequence of an underlying condition:

  • Sepsis (gram-negative bacteraemia most common, but any severe infection)
  • Major trauma and traumatic brain injury
  • Obstetric emergencies (amniotic fluid embolism, placental abruption, HELLP)
  • Malignancy (acute promyelocytic leukaemia particularly)
  • Massive transfusion and transfusion reactions
  • Burns, pancreatitis

Diagnosis

The ISTH scoring system uses four parameters: platelets, fibrinogen, prothrombin time, and D-dimer. A score ≥5 is consistent with overt DIC.

Laboratory findings: thrombocytopenia, prolonged PT and APTT, low fibrinogen, elevated D-dimer, blood film showing microangiopathic haemolytic anaemia (MAHA) with schistocytes.

Management

The priority is treatment of the underlying cause. Blood product support in patients who are bleeding or at high risk:

  • FFP 15 mL/kg to correct coagulopathy
  • Cryoprecipitate to raise fibrinogen above 1.5 g/L
  • Platelet transfusion if below 50 × 10⁹/L with bleeding, or below 20 × 10⁹/L without bleeding

Prophylactic correction in the absence of bleeding or planned procedures is not routinely recommended. Heparin may be considered in the predominantly thrombotic form (purpura fulminans, acral ischaemia) but is rarely used.

Tranexamic acid may be considered in DIC with primary fibrinolysis (traumatic DIC in particular), guided by thromboelastography.

Thrombotic Thrombocytopenic Purpura and HUS

TTP

TTP results from severe deficiency of ADAMTS13, the metalloprotease that cleaves ultra-large von Willebrand factor (ULvWF) multimers. In the absence of ADAMTS13, ULvWF accumulates and causes platelet-rich microthrombi in the microvasculature.

Acquired TTP results from autoimmune ADAMTS13 inhibition (IgG antibodies). Congenital TTP (Upshaw-Schulman syndrome) results from biallelic ADAMTS13 mutations.

Classic pentad: Thrombocytopenia, MAHA, fever, neurological symptoms (confusion, seizures, stroke), renal impairment. All five features are present in fewer than 10% of cases. The key diagnostic signal is thrombocytopenia plus MAHA — TTP should be assumed until proven otherwise, as delay in treatment is fatal.

The PLASMIC score (platelets, haemolysis labs, no active cancer, no stem cell transplant, MCV, INR, creatinine) stratifies the probability of ADAMTS13 deficiency before results are available.

Investigations: ADAMTS13 activity and inhibitor level (sent urgently but results may take days), blood film, LDH, haptoglobin, DAT (direct antiglobulin test — negative in TTP, distinguishing it from autoimmune haemolytic anaemia).

Management:

Plasma exchange (PEX) is the cornerstone of treatment and must not be delayed. PEX removes the ADAMTS13 inhibitor and replaces functional ADAMTS13 via donor plasma. Continue daily until platelet count normalises and LDH falls.

Caplacizumab (anti-vWF nanobody) reduces thrombus formation and accelerates platelet count recovery. It is now recommended in combination with PEX and immunosuppression in acquired TTP.

Corticosteroids (prednisolone 1 mg/kg/day) reduce autoantibody production.

Rituximab is used in relapsed or refractory acquired TTP to deplete B cells producing the ADAMTS13 antibody.

HUS

Haemolytic uraemic syndrome (HUS) shares the triad of MAHA, thrombocytopenia, and AKI with TTP but predominantly affects the kidneys.

Shiga toxin-mediated HUS (STEC-HUS): Caused by Shiga toxin-producing E. coli (most commonly O157:H7). Presents with bloody diarrhoea followed by HUS. Antibiotics are avoided as they may increase toxin release. Treatment is supportive; renal replacement therapy is often required. Recovery of renal function is usual in children.

Atypical HUS (aHUS): Results from dysregulation of the complement alternative pathway (mutations in complement regulatory proteins: CFH, CFI, MCP). Managed with eculizumab (anti-C5 monoclonal antibody), which is highly effective and has transformed the outlook. Plasma exchange has limited efficacy.

Tumour Lysis Syndrome

Tumour lysis syndrome (TLS) results from rapid release of intracellular contents following massive cell death, most commonly after initiating chemotherapy but occasionally spontaneously in high-burden malignancies.

Causes

High-risk conditions: Burkitt lymphoma, ALL, AML (particularly M3 — acute promyelocytic leukaemia), large B-cell lymphoma with high bulk.

Biochemical Features

  • Hyperkalaemia — the most immediately life-threatening consequence
  • Hyperphosphataemia — phosphate released from nucleotides
  • Hypocalcaemia — calcium-phosphate precipitation (metastatic calcification, seizures, arrhythmias)
  • Hyperuricaemia — from purine catabolism via xanthine oxidase to uric acid
  • AKI — from urate and calcium-phosphate precipitation in renal tubules

Management

Prevention is preferable to treatment. High-risk patients receive:

  • Allopurinol (xanthine oxidase inhibitor) — prevents new uric acid production but does not clear existing uric acid
  • Rasburicase (recombinant urate oxidase) — converts uric acid to allantoin, more soluble and rapidly cleared; preferred in high-risk or established TLS; contraindicated in G6PD deficiency (causes haemolysis)
  • Aggressive IV hydration to maintain high urine output

Treatment:

  • Hyperkalaemia: calcium gluconate (cardiac membrane stabilisation), insulin-dextrose, salbutamol, resonium, consideration of RRT if refractory
  • Hypocalcaemia: only treat if symptomatic — replacing calcium when phosphate is also high worsens precipitation
  • AKI: RRT may be required urgently, particularly in uric acid nephropathy

Hyperviscosity Syndrome

Hyperviscosity syndrome results from an increase in plasma viscosity from paraprotein accumulation, or from cellular hyperviscosity in polycythaemia and extreme leucocytosis.

Causes: Waldenström's macroglobulinaemia (IgM paraprotein — most common cause of plasma hyperviscosity), multiple myeloma (particularly IgA and IgG3), polycythaemia vera, extreme leucocytosis (>100 × 10⁹/L, usually AML or CML).

Features: Headache, visual disturbance (dilated retinal veins, haemorrhages — fundoscopy characteristically shows "sausage-link" veins), confusion, bleeding (impaired platelet function), heart failure, and in polycythaemia, thrombosis.

Management: Plasmapheresis or exchange transfusion for emergency management. Leukapheresis for symptomatic leucostasis. Definitive treatment of the underlying malignancy.

Blast Crisis

Blast crisis describes the transformation of a previously indolent haematological malignancy (CML, MDS) to acute leukaemia, defined by the presence of ≥20% blasts in the blood or marrow.

Complications requiring ICU admission: hyperleucocytosis (white cell count >100 × 10⁹/L) causing leucostasis (pulmonary and CNS microvascular obstruction), TLS, bleeding, and infection.

Management of leucostasis: Leukapheresis to acutely reduce white cell count; hydroxyurea for cytoreduction. Avoid red cell transfusion if WBC is very high (increases viscosity); transfuse platelets for bleeding. Definitive treatment is induction chemotherapy and subsequent allogeneic stem cell transplant.

Viva Questions

How do you differentiate TTP from DIC at the bedside?

Both conditions present with thrombocytopenia and features of microangiopathic haemolytic anaemia, but their mechanisms and management differ fundamentally. TTP results from ADAMTS13 deficiency causing platelet-rich microvascular thrombosis; coagulation factors are not consumed, so PT, APTT, and fibrinogen are normal or near-normal. DIC involves systemic coagulation activation with consumption of all haemostatic components; PT, APTT are prolonged, fibrinogen is low, and D-dimer is markedly elevated. Blood film in TTP typically shows more prominent schistocytes. Renal impairment is usual in TTP but not invariably so; neurological features are characteristic of TTP but can occur in severe DIC too. The presence of a known trigger for DIC (sepsis, trauma, obstetric emergency, malignancy) favours DIC. An ADAMTS13 level below 10% confirms TTP, but treatment should not wait for this result — the PLASMIC score guides empirical plasma exchange while results are pending.

What is the management of acute TTP in the ICU?

Plasma exchange must be started as soon as the diagnosis is suspected, without waiting for ADAMTS13 results. Delay significantly worsens mortality. Plasma exchange is performed daily using donor plasma (not albumin) as the replacement fluid, providing functional ADAMTS13 while removing the inhibitory autoantibody. Caplacizumab, an anti-vWF nanobody, is added to prevent new platelet-rich thrombus formation and reduces the time to platelet count normalisation and early mortality. Corticosteroids (prednisolone 1 mg/kg/day) are given to suppress autoantibody production. Rituximab is reserved for refractory or relapsing disease. Platelet transfusion is contraindicated unless there is life-threatening haemorrhage — transfused platelets are consumed in ongoing microvascular thrombosis and may worsen organ ischaemia. Response is assessed by daily platelet count and LDH; plasma exchange continues until the platelet count is above 150 × 10⁹/L for at least two consecutive days.

How do you recognise and manage tumour lysis syndrome?

TLS is recognised by the biochemical constellation of hyperkalaemia, hyperphosphataemia, hypocalcaemia, and hyperuricaemia — the Cairo-Bishop criteria. Laboratory TLS is defined as the presence of at least two of these abnormalities within three days of chemotherapy (or seven days before); clinical TLS additionally requires one of AKI, cardiac arrhythmia, or seizure. It most commonly follows treatment of high-burden haematological malignancies, particularly Burkitt lymphoma and ALL. In patients known to be at high risk, prevention is preferable: allopurinol or rasburicase (for very high-risk cases), aggressive IV hydration targeting a urine output above 2 mL/kg/hour, and ECG monitoring. Once TLS is established, the priorities are managing hyperkalaemia urgently (calcium gluconate for cardiac stabilisation, insulin-dextrose, consideration of early renal replacement therapy if severe), treating symptomatic hypocalcaemia with great caution given the risk of calcium-phosphate precipitation, and maintaining renal perfusion. Rasburicase reduces uric acid rapidly and is preferred over allopurinol in established TLS.