Hematology

«Blue-green crystals of death» and Döhle bodies in neutrophils

A clinical case of an 81-year-old woman with sepsis: critical blue-green inclusions in neutrophils, Knyazkov — Döhle bodies and what they mean for the prognosis.

«Blue-green crystals of death» and Döhle bodies in neutrophils

The clinical case was kindly provided by Darya Todzhaeva, physician in clinical laboratory diagnostics, Moscow.

Blood smear of a woman in intensive care

Critical blue-green inclusions, also known as blue-green neutrophilic inclusions and informally called «crystals of death», are amorphous blue-green cytoplasmic inclusions found in neutrophils and occasionally in monocytes.

They are found most often in critically ill patients, especially those with liver disease, and their presence in a peripheral blood smear is linked to high short-term mortality. The statistics show that 56 % of patients died soon after the inclusions were first seen — usually within two weeks.

The current view is that these critical green inclusions are most likely phagocytosed products of lysosomal degradation related to tissue injury.

Here is the case of an 81-year-old woman admitted to intensive care with a diagnosis of sepsis. Her blood smear showed both Döhle bodies and blue-green inclusions.

On the left a Döhle body in a white cell, on the right a critical blue-green inclusion in a neutrophil
A Döhle body in a white cell
Döhle bodies in a segmented neutrophil

What the full blood count showed #

Anaemia — haemoglobin 66 g/l, normocytic and normochromic, without anisocytosis. The reticulocyte count was 0.01 million/µl, which points to a hyporegenerative anaemia caused by suppressed erythropoiesis in the bone marrow.

Normoblasts appearing in the peripheral blood while the reticulocyte count is low may be due to disturbed bone marrow architecture or, more likely, to a large release of inflammatory mediators, mainly IL-6.

Thrombocytopenia — a platelet count of 27 thousand/µl, confirmed by microscopy of the smear. Since the anaemia is hyporegenerative, we can assume that the production of new platelets in the bone marrow is suppressed as well — a hypoplastic thrombocytopenia.

White cells — 8 thousand/µl, with a high proportion of band neutrophils (13 %) and with earlier precursors present: myelocytes 10 %, metamyelocytes 2 %. This may well be the result of the intense inflammatory reaction of sepsis, or of chronic myeloid leukaemia.

Lymphocytopenia — 1.04 thousand/µl, another marker of a critically ill patient.

The full blood count with the differential of the woman with sepsis

Knyazkov — Döhle bodies #

Knyazkov — Döhle bodies are single or multiple pale blue cytoplasmic inclusions, the remnants of rough endoplasmic reticulum.

Other, less conspicuous Döhle bodies were found in this woman’s smear as well.

A Döhle body in a neutrophil of the woman with sepsis

The bodies are named after the German pathologist Karl Gottfried Paul Döhle (1855–1928). They are seen in bacterial infections, after tissue injury including burns, in inflammation, after G-CSF administration, in neutrophilic leukaemoid reactions and during pregnancy.

A Döhle body in a neutrophil of the 81-year-old woman from intensive care

May — Hegglin anomaly #

There is also a benign inherited condition known as the May — Hegglin anomaly, with a similar but not identical morphology. Here the inclusions tend to be larger and more angular, and they occur in every type of white cell except lymphocytes.

Such inclusions are called pseudo-Döhle bodies and are seen in an inherited group of disorders known collectively as MYH9-related. The typical features of the MYH9 syndromes are thrombocytopenia, macrothrombocytes in the smear and inclusions in the neutrophils.

A slide from the lesson «Platelet morphology»

Acknowledgements #

Thank you to the founder of the «Leukoformula» project, Evgeny Zaytsev, physician in clinical laboratory diagnostics, for his kind help with publishing this article and interpreting the data.